Hiroshi Nonogi

Effectiveness of Bystander-Initiated Cardiac-Only Resuscitation for Patients With Out-of-Hospital Cardiac Arrest

Background— Previous animal and clinical studies suggest that bystander-initiated cardiac-only resuscitation may be superior to conventional cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrests. Our hypothesis was that both cardiac-only bystander resuscitation and conventional bystander CPR would improve outcomes from out-of-hospital cardiac arrests of ≤15 minutes’ duration, whereas the addition of rescue breathing would improve outcomes for cardiac arrests lasting >15 minutes. Methods and Results— We carried out a prospective, population-based, observational study involving consecutive patients with emergency responder resuscitation attempts from May 1, 1998, through April 30, 2003. The primary outcome measure was 1-year survival with favorable neurological outcome. Multivariable logistic regression analysis was performed to evaluate the relationship between type of CPR and outcomes. Among the 4902 witnessed cardiac arrests, 783 received conventional CPR, and 544 received cardiac-only resuscitation. Excluding very-long-duration cardiac arrests (>15 minutes), the cardiac-only resuscitation yielded a higher rate of 1-year survival with favorable neurological outcome than no bystander CPR (4.3% versus 2.5%; odds ratio, 1.72; 95% CI, 1.01 to 2.95), and conventional CPR showed similar effectiveness (4.1%; odds ratio, 1.57; 95% CI, 0.95 to 2.60). For the very-long-duration arrests, neurologically favorable 1-year survival was greater in the conventional CPR group, but there were few survivors regardless of the type of bystander CPR (0.3% [2 of 624], 0% [0 of 92], and 2.2% [3 of 139] in the no bystander CPR, cardiac-only CPR, and conventional CPR groups, respectively; P<0.05). Conclusions— Bystander-initiated cardiac-only resuscitation and conventional CPR are similarly effective for most adult out-of-hospital cardiac arrests. For very prolonged cardiac arrests, the addition of rescue breathing may be of some help.

Plasma MicroRNA 499 as a Biomarker of Acute Myocardial Infarction

BACKGROUND MicroRNAs (miRNAs) are endogenous small RNAs 21-25 nucleotides in length. Recently, we reported that miRNA 208 (miR-208) is produced exclusively in the rat myocardium and that plasma miR-208 is a biomarker of myocardial injury in rats. In the present study, we assessed the hypothesis that plasma concentrations of myocardial-specific miRNAs can be used to diagnose myocardial injury in humans. METHODS We used array analysis of miRNA production in various human tissues to identify heart-specific miRNAs. We assessed the plasma concentrations of miR-499 in 14 individuals with acute coronary syndromes, 15 individuals with congestive heart failure, and 10 individuals without cardiovascular diseases. Plasma miR-499 concentrations were measured with a real-time reverse-transcription PCR method that used an artificial small RNA as an internal calibrator. RESULTS The miRNA array analysis of various human tissues indicated that miR-499 was produced almost exclusively in the heart. Plasma miR-499 concentrations were measurably increased in all individuals with acute myocardial infarction but were below the limit of detection for all individuals in the other patient groups. CONCLUSIONS The plasma concentration of miR-499 may be a useful biomarker of myocardial infarction in humans.

Continuous Improvements in “Chain of Survival” Increased Survival After Out-of-Hospital Cardiac Arrests A Large-Scale Population-Based Study

Background— The impact of ongoing efforts to improve the “chain of survival” for out-of-hospital cardiac arrest (OHCA) is unclear. The objective of this study was to evaluate the incremental effect of changes in prehospital emergency care on survival after OHCA. Methods and Results— This prospective, population-based observational study involved consecutive patients with OHCA from May 1998 through December 2006. The primary outcome measure was 1-month survival with favorable neurological outcome. Multiple logistic regression analysis was used to assess factors that were potentially associated with better neurological outcome. Among 42 873 resuscitation-attempted adult OHCAs, 8782 bystander-witnessed arrests of presumed cardiac origin were analyzed. The median time interval from collapse to call for medical help, first cardiopulmonary resuscitation, and first shock shortened from 4 (interquartile range [IQR] 2 to 11) to 2 (IQR 1 to 5) minutes, from 9 (IQR 5 to 13) to 7 (IQR 3 to 11) minutes, and from 19 (IQR 13 to 22) to 9 (IQR 7 to 12) minutes, respectively. Neurologically intact 1-month survival after witnessed ventricular fibrillation increased from 6% (6/96) to 16% (49/297; P<0.001). Among all witnessed OHCAs, earlier cardiopulmonary resuscitation (odds ratio per minute 0.89, 95% confidence interval 0.85 to 0.93) and earlier intubation (odds ratio per minute 0.96, 95% confidence interval 0.94 to 0.99) were associated with better neurological outcome. For ventricular fibrillation, only earlier shock was associated with better outcome (odds ratio 0.84, 95% confidence interval 0.80 to 0.88). Conclusions— Data from a large, population-based cohort demonstrate a continuous increase in OHCA survival with improvement in the chain of survival. The incremental benefit of early advanced care on OHCA survival is also suggested.

Percutaneous transluminal coronary angioplasty of chronic total occlusions. determinants of primary success and long-term clinical outcome

This study was conducted to assess the determinants of the procedural success and long‐term clinical benefits of percutaneous transluminal balloon angioplasty (PTCA) of chronic total occlusion (CTO) in recent years. Two hundred and twenty‐six consecutive patients who underwent PTCA of CTO were divided into two groups according to the procedural success (n = 134) or failure (n = 92). Both groups were analyzed in terms of the initial success, predictors of procedural failure, and clinical outcome. The procedural success rate was noted to have improved to more than 70% since 1995. A multiple logistic regression analysis revealed that the presence of calcification, the length of the occlusion and the presence of multivessel disease were independent predictors of procedural failure. Cardiac death and the need for coronary surgery were significantly less frequent in patients with procedural success than in those with procedural failure. In properly selected cases, the success rate of PTCA of CTO is acceptable. Long‐term clinical benefit is suggested by the high rate of freedom from coronary surgery and the low cardiac death rate in the patients who underwent successful revascularization. Cathet. Cardiovasc. Intervent. 49:258–264, 2000.

Nationwide Improvements in Survival From Out-of-Hospital Cardiac Arrest in Japan

Background—Little is known about the nationwide trend in the survival of out-of-hospital cardiac arrest (OHCA) in Japan and the differences in incidence and survival by age group and origin of arrest. Methods and Results—A nationwide, prospective, population-based observation covering the whole population of Japan and involving consecutive OHCA patients with resuscitation attempts was conducted from January 2005 to December 2009. The main outcome measure was 1-month survival with favorable neurological outcome. The nationwide trends in OHCA incidence and outcome by age and origin of arrest were assessed. Multiple logistic regression analysis for bystander-witnessed OHCA was used to adjust for factors that were potentially associated with favorable neurological outcome. During 5 years, 547 153 overall OHCAs and 169 360 bystander-witnessed OHCAs were enrolled. The annual incidence significantly increased among overall OHCAs and bystander-witnessed OHCAs. Neurologically favorable survival significantly increased from 1.6% (1676/102 737) in 2005 to 2.8% (3280/115 250) in 2009 (P<0.001), from 2.1% (638/30 556) to 4.3% (1558/36 361) (P<0.001), and from 9.8% (437/4461) to 20.6% (1215/5906) (P<0.001) among overall OHCA, bystander-witnessed OHCA, and bystander-witnessed ventricular fibrillation OHCA, respectively. Public-access automated external defibrillator use, either bystander-initiated chest compression–only cardiopulmonary resuscitation or conventional cardiopulmonary resuscitation, and earlier emergency medical services response time were associated with a better neurological outcome. Favorable neurological outcome among adult OHCA subjects significantly improved, but the outcome among younger children and very elderly subjects did not improve and was poor irrespective of origin of OHCA. Conclusions—Nationwide improvements of favorable neurological outcome from OHCA were observed in Japan and differed by age group and origin of OHCA.

Plasma brain natriuretic peptide is a biochemical marker for the prediction of progressive ventricular remodeling after acute myocardial infarction

To investigate the relation between plasma brain natriuretic peptide (BNP) and progressive ventricular remodeling, we measured plasma BNP and atrial natriuretic peptide (ANP) in 30 patients with acute myocardial infarction on days 2, 7, 14, and 30 after the onset. Left ventricular end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and ejection fraction (EF) on admission and 1 month after the onset were assessed by left ventriculography. Changes in EDVI (deltaEDVI), ESVI (deltaESVI), and EF (deltaEF) were obtained by subtracting respective acute-phase values from corresponding chronic-phase values. Plasma ANP on days 2 and 7 showed only weak correlations with deltaEDVI (r = 0.48 and 0.54; both p < 0.01), whereas plasma BNP on day 7 more closely correlated with deltaEDVI (r = 0.77; p < 0.001). When study patients were divided into two groups according to plasma BNP on day 7, the group with BNP higher than 100 pg/ml showed greater increases in left ventricular volume and less improvement in EF compared with the other group with BNP lower than 100 pg/ml (deltaEDVI = 10.4 +/- 8 vs -3.4 +/- 9 ml/m2, deltaESVI = 6.2 +/- 7 vs -4.9 +/- 5 ml/m2, and deltaEF = 1.0% +/- 4% vs 4.9% +/- 5%; p < 0.05, respectively). Multiple regression analysis revealed that only plasma BNP on day 7, but not ANP, peak creatine phosphokinase level, left ventricular end-diastolic pressure, or acute-phase EF, correlated independently with deltaEDVI (p < 0.01). These results suggest that plasma BNP may be a simple and useful biochemical marker for the prediction of progressive ventricular remodeling within the first 30 days of acute myocardial infarction.

Unblinded Pilot Study of Autologous Transplantation of Bone Marrow Mononuclear Cells in Patients With Thromboangiitis Obliterans

Background— The short-term clinical benefits of bone marrow mononuclear cell transplantation have been shown in patients with critical limb ischemia. The purpose of this study was to assess the long-term safety and efficacy of bone marrow mononuclear cell transplantation in patients with thromboangiitis obliterans. Methods and Results— Eleven limbs (3 with rest pain and 8 with an ischemic ulcer) of 8 patients were treated by bone marrow mononuclear cell transplantation. The patients were followed up for clinical events for a mean of 684±549 days (range 103 to 1466 days). At 4 weeks, improvement in pain was observed in all 11 limbs, with complete relief in 4 (36%). Pain scale (visual analog scale) score decreased from 5.1±0.7 to 1.5±1.3. An improvement in skin ulcers was observed in all 8 limbs with an ischemic ulcer, with complete healing in 7 (88%). During the follow-up, however, clinical events occurred in 4 of the 8 patients. The first patient suffered sudden death at 20 months after transplantation at 30 years of age. The second patient with an incomplete healing of a skin ulcer showed worsening of the lesion at 4 months. The third patient showed worsening of rest pain at 8 months. The last patient developed an arteriovenous shunt in the foot at 7 months, which spontaneously regressed by 1 year. Conclusions— In the present unblinded and uncontrolled pilot study, long-term adverse events, including death and unfavorable angiogenesis, were observed in half of the patients receiving bone marrow mononuclear cell transplantation. Given the current incomplete knowledge of the safety and efficacy of this strategy, careful long-term monitoring is required for future patients receiving this treatment.

Changes in diastolic properties of the regional myocardium during pacing-induced ischemia in human subjects.

Mechanisms related to alterations in the diastolic properties of the left ventricle during angina were studied in seven patients with coronary artery disease. Single plane left ventriculograms were obtained using a high fidelity micromanometer-tipped catheter in both the resting state and immediately after rapid cardiac pacing. In all patients, typical anginal pain developed with pacing stress. After atrial pacing, the left ventricular end-diastolic pressure increased from 10 +/- 3 to 21 +/- 7 mm Hg (+/- standard deviation) (p less than 0.005) regardless of the changes in the end-diastolic volume. The ejection fraction was reduced from 59 +/- 10 to 48 +/- 13% (p less than 0.05). The diastolic pressure-volume curves shifted upward in post-pacing beats in four patients, while in three the curves shifted more to the right. The regional myocardial function was expressed in quantitative terms by a radial coordinate system with the origin at the center of gravity of the end-diastolic silhouette. Two representative radial grids for normal and ischemic segments were selected. In the normal segment, the end-diastolic length was augmented by 15% (p less than 0.005) and was associated with a 24% increase in stroke excursion with pacing stress (p less than 0.05). The increase in diastolic pressure was accompanied by comparable increases in end-diastolic length, and the diastolic pressure-length relation moved up to the higher portion of the single curve. In the ischemic segment, the end-diastolic length remained unchanged in the post-pacing beat, but segment shortening was significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic variants in PCSK9 affect the cholesterol level in Japanese

AbstractMutations in the proprotein convertase subtilisin/kexin 9 (PCSK9) gene have been reported in affected members of two families with autosomal dominant hypercholesterolemia. To investigate the effects of common variants in PCSK9 on the cholesterol level, we conducted an association study using a large cohort representing the general population in Japan (n=1,793). Direct sequencing in all of the exonic regions identified 21 polymorphisms. After consideration of linkage disequilibrium among these polymorphisms, we selected and genotyped nine polymorphisms by the TaqMan method. The intron 1/C(-161)T and exon 9/I474 V polymorphisms were associated with levels of total cholesterol (TC) [C(-161)T, P=0.0285; I474 V, P=0.0069] and low-density lipoprotein cholesterol (LDL-C) [C(-161)T, P=0.0257; I474 V, P=0.0007]. The distributions of these polymorphisms in subjects with miocardial infarction (MI) (n=649) were not different from those in the control population. These results provide the first evidence that common variants intron 1/C(-161)T and exon 9/I474 V in PCSK9 significantly affect TC and LDL-C levels in the general population in Japan.

Enhanced secretion of cardiac hepatocyte growth factor from an infarct region is associated with less severe ventricular enlargement and improved cardiac function

OBJECTIVES We hypothesized that the hepatocyte growth factor (HGF) may play a cardioprotective role in human myocardial infarction (MI). BACKGROUND The HGF is a novel, multifunctional growth factor implicated in wound healing, angiogenesis and promotion of cell survival. Recent animal studies have demonstrated the existence of an HGF system in the heart, where it is activated in response to myocardial ischemia and reperfusion. METHODS We studied 40 patients with acute myocardial infarction (AMI), who underwent coronary reperfusion therapy upon admission. Approximately four weeks later, left ventricular (LV) catheterization was repeated to determine the LV ejection fraction (EF), end-diastolic volume index (EDVI) and pressure (EDP). The levels of HGF and brain natriuretic peptide (BNP) were measured by collecting blood samples from cardiac veins draining the infarcted region (MI region) and those draining the noninfarcted region (non-MI region). The ratio of the HGF level in the MI region to that in the non-MI region (= MI/non-MI ratio) was calculated in each patient as an index of the MI-related HGF secretion. The MI/non-MI ratio for BNP was also calculated. RESULTS The MI/non-MI ratio for HGF correlated inversely with LVEDP (r = -0.644, p < 0.0001) and LVEDVI (r = -0.843, p < 0.0001) and positively with LVEF (r = 0.763, p < 0.0001). These correlations were completely opposite in direction from those for BNP and LVEDP (r = 0.678, p < 0.0001), LVEDVI (r = 0.783, p < 0.0001) and LVEF (r = -0.805, p < 0.0001). These findings indicate that cardiac HGF acts in contrast to BNP, a biochemical marker for the development of LV remodeling. CONCLUSIONS Enhanced secretion of cardiac HGF from the MI region is associated with an attenuation of ventricular enlargement and an improvement in cardiac function. The HGF system may modulate the process of ventricular remodeling and thus have important clinical implications.