Institutional Characteristics and Prognosis of Acute Myocardial Infarction With Cardiogenic Shock in Japan　- Analysis From the JROAD/JROAD-DPC Database.

BACKGROUND: The high mortality of acute myocardial infarction (AMI) with cardiogenic shock (i.e., Killip class IV AMI) remains a challenge in emergency cardiovascular care. This study aimed to examine institutional factors, including the number of JCS board-certified members, that are independently associated with the prognosis of Killip class IV AMI patients.Methods and Results:In the Japanese registry of all cardiac and vascular diseases-diagnosis procedure combination (JROAD-DPC) database (years 2012-2016), the 30-day mortality of Killip class IV AMI patients (n=21,823) was 42.3%. Multivariate analysis identified age, female sex, admission by ambulance, deep coma, and cardiac arrest as patient factors that were independently associated with higher 30-day mortality, and the numbers of JCS board-certified members and of intra-aortic balloon pumping (IABP) cases per year as institutional factors that were independently associated with lower mortality in Killip class IV patients, although IABP was associated with higher mortality in Killip classes I-III patients. Among hospitals with the highest quartile (≥9 JCS board-certified members), the 30-day mortality of Killip class IV patients was 37.4%. CONCLUSIONS: A higher numbers of JCS board-certified members was associated with better survival of Killip class IV AMI patients. This finding may provide a clue to optimizing local emergency medical services for better management of AMI patients in Japan.

Prognostic Value of Neurological Status on Hospital Arrival for Short-Term Outcome in Patients With Cardiovascular Shock　- Sub-analysis of the Japanese Circulation Society Cardiovascular Shock Registry.

BACKGROUND: Consciousness disturbance is one of the major clinical signs associated with shock state, but its prognostic value has not been previously evaluated in cardiovascular shock patients. We aimed to evaluate the prognostic value of neurological status for 30-day mortality in cardiovascular shock patients without out-of-hospital cardiac arrest (OHCA). Methods and Results: Patients with out-of-hospital onset cardiovascular shock were recruited from the Japanese Circulation Society Shock Registry. Neurological status upon hospital arrival was evaluated using the Japan Coma Scale (JCS). Patients were divided into 4 groups according to the JCS: alert, JCS 0; awake, JCS 1-3 (not fully alert but awake without any stimuli); arousable, JCS 10-30 (arousable with stimulation); and coma JCS 100-300 (unarousable). The primary endpoint was 30-day all-cause death. In total, 700 cardiovascular shock patients without OHCA were assessed. The coma group was associated with a higher incidence of 30-day all-cause death compared with other groups (alert, 15.3%; awake, 24.4%; arousable, 36.8%; coma, 48.5%, P<0.001). Similar trends were observed in etiologically divergent subgroups (acute coronary syndrome, non-ischemic arrhythmia, and aortic disease). On multivariate Cox regression analysis, arousable (hazard ratio [HR], 1.82; 95% CI: 1.16-2.85, P=0.009) and coma (HR, 2.72; 95% CI: 1.76-4.22, P<0.001) (reference: alert) independently predicted 30-day mortality. CONCLUSIONS: Neurological status upon hospital arrival was useful to predict 30-day mortality in cardiovascular shock patients without OHCA.

Clinical characteristics and prognostic factors in acute coronary syndrome patients complicated with cardiogenic shock in Japan: analysis from the Japanese Circulation Society Cardiovascular Shock Registry.

Cardiogenic shock frequently leads to death even with intensive treatment. Although the leading cause of cardiogenic shock is acute coronary syndrome (ACS), the clinical characteristics and the prognosis of ACS with cardiogenic shock in the present era still remain to be elucidated. We analyzed clinical characteristics and predictors of 30-day mortality in ACS with cardiogenic shock in Japan. The Japanese Circulation Society Cardiovascular Shock registry was a prospective, observational, multicenter, cohort study. Between May 2012 and June 2014, 495 ACS patients with cardiogenic shock were analyzed. The primary endpoint was 30-day all-cause mortality. The median [interquartile range; IQR] age was 71.0 [63.0, 80.0] years. The median [IQR] value of systolic blood pressure (SBP) and heart rate were 75.0 [50.0, 86.5] mm Hg and 65.0 [38.0, 98.0] bpm, respectively. Multivariable analysis showed an odds ratio (OR) of 4.76 (confidence intervals; CI 1.97-11.5, p < 0.001) in the lowest SBP category (< 50 mm Hg) for SBP ≥ 90 mm Hg. Moreover, age per 10 years increase (OR 1.38, CI 1.18-1.61, p = 0.002), deep coma (OR 3.49, CI 1.94-6.34, p < 0.001), congestive heart failure (OR 3.81, CI 2.04-7.59, p < 0.001) and left main trunk disease (LMTD) (OR 2.81, CI 1.55-5.10, p < 0.001) were independent predictors. Severe hypotension, older age, deep coma, congestive heart failure, and LMTD were independent unfavorable factors in ACS complicated by cardiogenic shock in Japan. A prompt assessment of high-risk patients referring to those predictors in emergency room could lead to appropriate treatment without delay.

Characterization of three strains of Capnocytophaga canis isolated from patients with sepsis.

Capnocytophaga canimorsus and Capnocytophaga cynodegmi, both commensal bacteria in the oral cavities of dogs and cats, are zoonotic pathogens. In particular, C. canimorsus causes sepsis and fatal septic shock. Recently, a novel Capnocytophaga species, C. canis, was isolated from the oral cavities of healthy dogs. It is reportedly oxidase-negative and therefore considered avirulent in humans. In the present study, three strains of C. canis were isolated from Japanese patients with sepsis. All three strains, HP20001, HP33001 and HP40001, were oxidase-positive. Nucleotide sequence identities of the 16S rRNA gene of the three strains to the C. canimorsus type strain ATCC35979, C. cynodegmi type strain ATCC49044 and C. canis type strain LMG29146 were 96.9-97.0%, 96.9-97.0% and 99.7-99.8%, respectively. Multi-locus sequence analysis based on seven house-keeping genes, dnaJ, fumC, glyA, gyrB, murG, trpB and tuf, revealed that the oxidase-positive C. canis strains isolated in Japan and oxidase-negative strains of C. canis from canine oral cavities in Switzerland were clustered in different genetic subgroups. These results indicate that the virulence of C. canis strains in humans is associated with oxidase activity.

Characteristics and Predictors of Mortality in Patients With Cardiovascular Shock in Japan　- Results From the Japanese Circulation Society Cardiovascular Shock Registry.

BACKGROUND: There are little data about cardiovascular shock caused by various diseases. We evaluated the characteristics and predictors of 30-day mortality in patients with cardiovascular shock in Japan. METHODS AND RESULTS: The Japanese Circulation Society Cardiovascular Shock registry was a prospective, observational, multicenter, cohort study. Between May 2012 and June 2014, 979 patients with cardiovascular shock were analyzed. The primary endpoint was 30-day all-cause mortality. The mean systolic blood pressure on hospital arrival was 78±18 mmHg. The main causes of shock were acute coronary syndrome (51.0%), non-ischemic arrhythmia (16.4%), and aortic disease (14.9%). The 30-day all-cause mortality was 34.3%. After adjustment for independent predictors of 30-day mortality, the odds ratios for systolic blood pressure (per 10-mmHg decrease), consciousness disturbance, congestive heart failure, out-of-hospital cardiac arrest, estimated glomerular filtration rate (per 10-ml/min/1.73 m(2)decrease), and causes of shock (non-ischemic arrhythmia, aortic disease, and myocarditis) were 1.15 (95% confidence interval [CI], 1.08-1.22), 2.62 (95% CI, 1.80-3.82), 2.58 (95% CI, 1.67-3.99), 1.62 (95% CI, 1.05-2.51), 1.20 (95% CI, 1.10-1.30), and 0.48 (95% CI, 0.30-0.77), 3.98 (95% CI, 2.32-6.81), and 3.25 (95% CI, 1.20-8.84), respectively. CONCLUSIONS: The 30-day mortality for cardiovascular shock was still high at 34%. Primary predictors of mortality were cardiorenal function on hospital arrival and shock etiology.

Home-based cardiac rehabilitation decreases red cell distribution width in chronic heart failure.

OBJECTIVE: Red cell distribution width (RDW) is a measure of variation in the volume of circulating erythrocytes and has recently emerged as a powerful prognostic marker in heart failure. We studied the effect of 5-month, home-based cardiac rehabilitation on RDW. METHODS AND RESULTS: Sixty-two patients (age: median 67 years, IQR 63-74) with chronic heart failure caused by reduced left ventricular systolic function were enrolled. Exercise time and physical activity levels out of the hospital were determined by a single-axial accelerometer. Baseline RDW values were: median 13.6, IQR 12.8-14.4%, with 13 patients (21.0%) showing values above the upper normal limit. RDW values were decreased significantly after training in the 13 patients with elevated baseline RDW values (P < 0.01), but not in the remaining 49 patients with normal baseline RDW values. There was a highly significant correlation between baseline RDW and changes in RDW after exercise training (P = 0.0001, r2 = 0.628, n = 62). The time spent for moderate (> 3 METs) exercise was: median 9.0, IQR 3.0-18.8 minutes per day. CONCLUSIONS: Relatively low intensity, home-based cardiac rehabilitation was associated with decreased RDW in heart failure patients with abnormal RDW.

The importance of daily physical activity for improved exercise tolerance in heart failure patients with limited access to centre-based cardiac rehabilitation.

BACKGROUND: Supervised cardiac rehabilitation provided at dedicated centres ameliorates exercise intolerance in patients with chronic heart failure. OBJECTIVE: To correlate the amount of physical activity outside the hospital with improved exercise tolerance in patients with limited access to centre-based programs. METHODS: Forty patients (median age 69 years) with stable heart failure due to systolic left ventricular dysfunction participated in cardiac rehabilitation once per week for five months. Using a validated single-axial accelerometer, the number of steps and physical activity-related energy expenditures on nonrehabilitation days were determined. RESULTS: Median (interquartile range) peak oxygen consumption was increased from 14.4 mL/kg/min (range 12.9 mL/kg/min to 17.8 mL/kg/min) to 16.4 mL/kg/min (range 13.9 mL/kg/min to 19.1 mL/kg/min); P<0.0001, in association with a decreased slope of the minute ventilation to carbon dioxide production plot (34.2 [range 31.3 to 38.1] versus 32.7 [range 30.3 to 36.5]; P<0.0001). Changes in peak oxygen consumption were correlated with the daily number of steps (P<0.01) and physical activity-related energy expenditures (P<0.05). Furthermore, these changes were significantly correlated with total exercise time per day and time spent for light (≤3 metabolic equivalents) exercise, but not with time spent for moderate/vigorous (>3 metabolic equivalents) exercise. CONCLUSIONS: The number of steps and energy expenditures outside the hospital were correlated with improved exercise capacity. An accelerometer may be useful for guiding home-based cardiac rehabilitation.

The Clinical Features and Outcomes of Patients with Takotsubo Syndrome: The Experience at an Emergency General Hospital.

Objective We aimed to elucidate clinical characteristics, contemporary practice and outcomes of patients with takotsubo syndrome who were hospitalized in an emergency general hospital with angiography capabilities. Methods This retrospective study included a total of 42 consecutive patients who were admitted between January 2010 and August 2014. Results The study population included 11 men (26%) and 31 women (74%) [median age 76 years (interquartile range, 66-83)]. Physical stress and emotional stress were identified as triggers in 28 (67%) patients and 5 (12%) patients, respectively. Electrocardiographic changes were observed in 41 (98%) patients, with ST-segment elevation being the most common (71%) finding. In-hospital complications occurred in 24 (57%) patients, and acute pulmonary congestion or cardiogenic shock was seen in 21 (50%) patients. Five patients died during hospitalization (in-hospital mortality: 12%). Conclusion Takotsubo syndrome was associated with significant morbidity and mortality among elderly patients who were treated at an emergency general hospital. Physicians and surgeons in all departments should be aware of the condition, especially in acutely ill subjects.

Six-month aerobic exercise training ameliorates central sleep apnea in patients with chronic heart failure.

BACKGROUND: Sleep-disordered breathing (SDB) is common in patients with heart failure and carries an independent risk for poor long-term prognosis. We aimed to study the effects of supervised, aerobic exercise training for 6 months on SDB in patients with chronic heart failure. METHODS AND RESULTS: We enrolled 18 patients having both systolic dysfunction (left ventricular ejection fraction <45%) and SDB (apnea-hypopnea index [AHI] >10). The exercise group comprised 10 patients who participated in our cardiac rehabilitation program for 6 months, and the remaining 8 patients served as control. AHI (median [interquartile range]) was unchanged in the control group patients at 6-month intervals (30.4 [19.9-36.3] versus 36.6 [8.6-39.4], NS). In contrast, AHI was significantly decreased in the exercise group from 24.9 [19.2-37.1] to 8.8 [5.3-10.1] (P < .01). In the exercise group, the numbers of central sleep apnea per night was significantly decreased (152 [124-244] versus 50 [24-67], P < .01) after exercise training, but those of obstructive apnea/hypopnea were unchanged (42 [7-94] versus 18 [7-54], NS). In addition, exercise training significantly increased peak oxygen consumption and decreased minute ventilation to carbon dioxide production slope (both P < .01). CONCLUSIONS: Six-month, aerobic exercise training increased exercise capacity and improved central sleep apnea in patients with chronic heart failure from systolic dysfunction.

Contemporary practice and outcomes of an elderly cohort of Japanese patients with non-ST-elevation acute coronary syndrome in the era of routine early invasive strategy.

BACKGROUND: An early invasive strategy for patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) has been recommended. However, patients at greater risk including the elderly are more often managed conservatively. We aimed to elucidate contemporary practice and outcomes of patients with NSTE-ACS who were referred to our hospital located in Kitakyushu City, one of the most aging metropolises in Japan. METHODS: A total of 270 consecutive NSTE-ACS patients hospitalized between January 2012 and December 2014 were retrospectively studied. RESULTS: Median [interquartile range] age was 73 [64, 80]years. Coronary angiography was performed in 264 (98%) patients. Importantly, 75% and 89% underwent angiography within 24h and 72h after admission, respectively. Revascularization was done in 124 (79%). The all-cause, in-hospital mortality was 3.7% and was higher in patients aged ≥80years (8.5% vs. 2.0% in those aged <80years, p<0.0001). No patient developed major bleeding or stroke during hospitalization. Killip class IV at presentation (odds ratio [OR] 8.77, 95% confidence intervals [CI] 1.64-47.6) and left main trunk disease (OR 7.58, 95% CI 1.28-45.5) were independently associated with in-hospital death. These two variables and a high (≥140) GRACE score were associated with a higher 1-year mortality by Kaplan-Meier survival analysis (p<0.0001). CONCLUSIONS: An early invasive strategy was safely done in an elderly cohort of Japanese patients with NSTE-ACS. In addition to early invasive approach, a further therapeutic strategy, most probably targeting a shock status, is needed to improve both short- and long-term survival.

The Effects of the Habitual Consumption of Miso Soup on the Blood Pressure and Heart Rate of Japanese Adults: A Cross-sectional Study of a Health Examination.

Objective It is recommended that middle-aged and elderly individuals reduce their salt intake because of the high prevalence of hypertension. The consumption of miso soup is associated with salt intake, and the reduced consumption of miso soup has been recommended. Recent studies have demonstrated that the consumption of miso soup can attenuate an autonomic imbalance in animal models. However, it is unclear whether these results are applicable to humans. This study examined the cross-sectional association between the frequency of miso soup consumption and the blood pressure and heart rate of human subjects. Methods A total of 527 subjects of 50 to 81 years of age who participated in our hospital health examination were enrolled in the present study and divided into four groups based on the frequency of their miso soup consumption ([bowl(s) of miso soup/week] Group 1, <1; Group2, <4; Group3, <7; Group4, ≥7). The blood pressure levels and heart rates of the subjects in each group were compared. Furthermore, a multivariable analysis was performed to determine whether miso soup consumption was an independent factor affecting the incidence of hypertension or the heart rate. Results The frequency of miso soup consumption was not associated with blood pressure. The heart rate was, however, lower in the participants who reported a high frequency of miso soup consumption. A multivariable analysis revealed that the participants who reported a high frequency of miso soup consumption were more likely to have a lower heart rate, but that the consumption of miso soup was not associated with the incidence of hypertension. Conclusion These results indicate that miso soup consumption might decrease the heart rate, but not have a significant effect on the blood pressure of in middle-aged and elderly Japanese individuals.

Radiofrequency catheter ablation of premature ventricular complexes from right ventricular outflow tract improves left ventricular dilation and clinical status in patients without structural heart disease.

OBJECTIVES: The present study evaluated clinical benefits of radiofrequency catheter ablation (RFA) for premature ventricular complexes from right ventricular outflow tract (RVOT-PVC) in patients without structural heart disease. BACKGROUND: It is unknown whether PVC causes left ventricular (LV) dilation, which is a well-recognized precursor of LV dysfunction and heart failure, and whether eliminating PVC by RFA produces clinical benefits in patients with RVOT-PVC. METHODS: Frequency of PVC per total heart beats by 24-h Holter monitoring, left ventricular ejection fraction (LVEF), left ventricular end-diastolic internal dimension (LVDd), mitral regurgitation (MR) by echocardiogram, cardiothoracic ratio (CTR) by chest radiogram, and New York Heart Association (NYHA) functional class of 40 patients with RVOT-PVC without structural heart disease were evaluated before and 6 to 12 months after RFA. RESULTS: Before RFA, a subgroup of patients with frequent (>20%) PVC demonstrated significantly enlarged LVDd and CTR, reduced LVEF, increased MR, and deteriorated NYHA functional class as compared to the subgroup with rare (<20%) PVC (54 +/- 1 mm vs. 45 +/- 1 mm, 52 +/- 2% vs. 46 +/- 1%, 66 +/- 2% vs. 73 +/- 2%, 1.2 +/- 0.2 degree vs. 0.4 +/- 0.1 degree, and 1.8 +/- 0.2 vs. 1.3 +/- 0.1, respectively; p < 0.05). Furthermore, ablating RVOT-PVC readily produced the improvement of all these abnormalities (47 +/- 1 mm, 41 +/- 1%, 72 +/- 2%, 0.3 +/- 0.1 degree, and 1.0 +/- 0.0, respectively; p < 0.05 compared with before RFA). CONCLUSIONS: These findings suggest that frequent (>20%) RVOT-PVC may be a possible cause of LV dysfunction and/or heart failure, and RFA produces clinical benefits in these patients.

Suppression of coronary artery spasm by the Rho-kinase inhibitor fasudil in patients with vasospastic angina.

BACKGROUND: Increased activity of Rho-kinase causes hypercontraction of vascular smooth muscle and has been implicated as playing a pathogenetic role in divergent cardiovascular diseases such as coronary artery spasm. We examined whether an intracoronary infusion of fasudil, a selective Rho-kinase inhibitor, would attenuate coronary vasoconstrictor responses to acetylcholine (ACh) in patients with vasospastic angina. METHODS AND RESULTS: We studied 20 consecutive patients in whom coronary artery spasm was provoked by intracoronary ACh. The patients underwent a second ACh challenge after pretreatment with intracoronary saline (n=5) or fasudil (n=15; 300 microg/min for 15 minutes). Angina and coronary vasospasm were reproducibly induced by the second testing in patients who received saline. In contrast, fasudil markedly attenuated the coronary constriction induced by ACh (P<0.001) and prevented the occurrence of chest pain and ischemic ECG changes in all treated patients (both P<0.01 versus saline). Fasudil, at the dose used in this study, did not significantly change systemic hemodynamics or baseline coronary blood flow. CONCLUSIONS: Fasudil was effective in preventing ACh-induced coronary artery spasm and resultant myocardial ischemia in patients with vasospastic angina. We suggest that this Rho-kinase inhibitor may be a novel therapeutic intervention to treat ischemic coronary syndromes caused by coronary artery spasm.

Rho-kinase inhibition with intracoronary fasudil prevents myocardial ischemia in patients with coronary microvascular spasm.

OBJECTIVES: We sought to determine whether a potent Rho-kinase inhibitor fasudil prevents the occurrence of myocardial ischemia in patients with microvascular angina attributable to coronary microvascular spasm. BACKGROUND: Effective treatment of patients with angina who have normal coronary arteriograms (microvascular angina) has not yet been established. Rho-kinase-mediated calcium sensitization of the myosin light chain in smooth muscle cells has been implicated as substantially contributing to vascular hyperconstriction. METHODS: We studied consecutive 18 patients with angina and normal epicardial coronaries in whom intracoronary acetylcholine (ACh) induced myocardial ischemia (ischemic electrocardiographic changes, myocardial lactate production, or both) without angiographically demonstrable epicardial coronary vasospasm. All patients underwent a second ACh challenge test after pretreatment with either saline (n = 5) or fasudil (4.5 mg intracoronarily, n = 13). RESULTS: Myocardial ischemia was reproducibly induced by ACh in the saline group. In contrast, 11 of the 13 patients pretreated with fasudil had no evidence of myocardial ischemia during the second infusion of ACh (p < 0.01). The lactate extraction ratio (median value [interquartile range]) during ACh infusion was improved by fasudil pretreatment, from -0.16 (-0.25 to 0.04) to 0.09 (0.05 to 0.18) (p = 0.0125). CONCLUSIONS: Fasudil ameliorated myocardial ischemia in patients who were most likely having coronary microvascular spasm. The inhibition of Rho-kinase may be a novel therapeutic strategy for this group of patients with microvascular angina.

Coronary microvascular spasm causes myocardial ischemia in patients with vasospastic angina.

OBJECTIVES: We aimed to test the hypothesis that coronary microvascular spasm (MVS) alone causes myocardial ischemia in patients with angina attributable to epicardial coronary spasm, and to determine whether there is a difference in clinical characteristics between those with and without microvascular spasm. BACKGROUND: Patients with "vasospastic angina" have epicardial coronary artery spasm, but it is unknown whether coronary microvessel disease also contributes to the occurrence of angina in these patients. METHODS: We studied 55 consecutive patients with angina in whom epicardial coronary spasm was provoked by intracoronary acetylcholine (ACH). RESULTS: In 14 patients (25.5%, Group 1), submaximal dose of ACH induced myocardial ischemia (chest pain, ischemic electrocardiogram changes, lactate production) without large epicardial spasm, suggesting the occurrence of coronary microvascular spasm. By contrast, the remaining 41 patients (Group 2) had evidence of myocardial ischemia only when epicardial spasm was angiographically demonstrated. The Group 1 patients were predominantly women (p < 0.05) and had a history of prolonged (>30 min) chest pain (p < 0.05), whereas the Group 2 patients were more likely men and smokers (p < 0.01). CONCLUSIONS: Myocardial ischemia most probably due to coronary MVS was demonstrated in a sizable portion of patients with epicardial vasospasm, preferentially in women having both typical and prolonged anginal pain. The result suggests that coronary microvascular disease may also contribute to angina in patients with "vasospastic angina."