Clinical implications of midventricular obstruction and intravenous propranolol use in transient left ventricular apical ballooning (Tako-tsubo cardiomyopathy).

BACKGROUND: Persistent hypotension with dynamic midventricular obstruction (MVO) in patients with transient left ventricular (LV) apical ballooning (Tako-tsubo cardiomyopathy) is an important complication that needs to be treated. PURPOSE: The objective of this study is to determine the effects of intravenous propranolol challenge on MVO in transient LV apical ballooning. SUBJECTS AND METHODS: Thirty-four patients (12 males, 22 females, mean age 64 +/- 17 years, age range 22-84 years) with LV apical ballooning were enrolled. The hemodynamic and echocardiographic effects of propranolol (0.05 mg/kg, maximum 4 mg) were analyzed in 13 patients. RESULTS: (1) Midventricular obstruction was present in 8 (24%) of 34 patients, and the pressure gradient (PG) ranged from 28 to 140 mm Hg. (2) Patients with MVO had similar demographic and clinical characteristics (symptoms, peak creatine kinase, plasma catecholamine levels) as those without MVO; however, in patients with MVO, abnormal Q waves on electrocardiogram and hypotension were more prevalent. (3) In the MVO group, intravenous propranolol changed the PG from 90 +/- 42 to 22 +/- 9 mm Hg, the systolic blood pressure (SBP) from 85 +/- 11 to 116 +/- 20 mm Hg, and the LV ejection fraction (LVEF) from 30% +/- 7% to 43% +/- 4%. (4) In all subjects, the changes in the PG after propranolol injection had a significant linear correlation with the SBP and LVEF changes: deltaSBP = 4.738 + 0.315 x deltaPG (r = 0.689 (P < .001) and deltaLVEF = 2.973 + 0.1321 x deltaPG (r = 0.715, P < .001). CONCLUSION: Intravenous propranolol is useful for treating dynamic MVO in patients with transient LV apical ballooning.

Noninvasive assessment of left atrial function by strain rate imaging in patients with hypertension: a possible beneficial effect of renin-angiotensin system inhibition on left atrial function.

Renin-angiotensin system (RAS) inhibitors are likely to reduce the development of atrial fibrillation by preventing atrial fibrosis. Strain rate (SR) imaging is a novel echocardiographic technique to quantify left atrial (LA) function. However, it has not been determined whether SR imaging is applicable for detection of LA dysfunction in hypertensive (HT) patients. We used SR imaging to assess alteration in LA function in HT patients and its modification by RAS inhibitors. SR imaging was performed in 80 HT patients and 50 age-matched normotensive (NT) subjects. HT patients were divided into two groups according to left ventricular hypertrophy (LVH) and LA dilatation. Peak SR was measured at each LA segment (septal, lateral, posterior, anterior, and inferior) and mean peak systolic SR (SR-LAs) was calculated by averaging data in each segment. Mean SR-LAs levels in the dilated LA group (1.97+/-0.45 s(-1), n=25) and non-dilated LA group (2.15+/-0.57 s(-1), n=55) were significantly (p<0.05) lower than that in NT subjects (2.53+/-0.71 s(-1)). Irrespective of the presence or absence of LVH, mean SR-LAs in HT patients was lower than that in NT subjects. When RAS inhibitors were used, the mean SR-LAs level in the non-dilated LA group was equivalent to that in NT subjects. In HT patients, mean SR-LAs, an index of LA reservoir function, decreases before development of LA enlargement and LVH. Treatment with RAS inhibitors appears to preserve LA reservoir function in HT patients without dilated LA. SR imaging can detect LA dysfunction in HT patients and is useful for evaluation of the therapeutic benefit on LA reservoir function.

Persistent insulin-sensitizing effects of sarpogrelate hydrochloride, a serotonin 2A receptor antagonist, in patients with peripheral arterial disease.

BACKGROUND: There is considerable interest in the pleiotropic pharmacological action of sarpogrelate hydrochloride, a novel selective serotonin 2A receptor antagonist. In the present study the persistent insulin-sensitizing effects of sarpogrelate were investigated in non-diabetic and non-medicated diabetic patients with peripheral artery disease (PAD). METHODS AND RESULTS: Indices of insulin resistance (IR) (fasting immunoreactive insulin (IRI) and calculated homeostasis model assessment (HOMA-R)) and adiponectin were measured before and after 2 weeks of sarpogrelate administration (300 mg/day) in 24 patients (19 men, 76+/-9 years) with PAD. Sixteen of the 24 patients were examined after 3 months of treatment for assessment of the chronic effect of sarpogrelate on IR. After 2 weeks of treatment, significant decreases in fasting IRI (p=0.03) and HOMA-R (p=0.024), but not in adiponectin, were observed. After 3 months of treatment, significant decreases in fasting IRI (16.0+/-10.3 vs 9.2+/-2.0 microU/ml, p=0.03) and HOMA-R (4.30+/-2.83 vs 2.40+/-0.74, p=0.025) were maintained. Furthermore, adiponectin was significantly increased (8.11+/-4.13 vs 9.64+/-4.37 microg/ml, p=0.027). All of the examined HOMA-R had a significant correlation with all of the examined adiponectin (p<0.001, r=-0.441). CONCLUSIONS: Sarpogrelate has a persistent insulin-sensitizing effect through adiponectin modification and might be beneficial for anti-atherosclerotic therapy, at least, in non-diabetic and non-medicated diabetic patients with PAD.

Long-term outcome after primary stenting versus balloon angioplasty for acute myocardial infarction.

The objective of the present prospective multicenter case-control study was to investigate the long-term clinical outcome (5 years) of primary stenting compared to primary percutaneous transluminal coronary angioplasty (PTCA) without stenting (POBA) in patients with acute myocardial infarction at 7 cardiovascular centers in Hokkaido, Japan. Forty-one patients with acute myocardial infarction treated with successful primary stenting (stent group: case) and paired with 41 matched control subjects with acute myocardial infarction treated by successful primary PTCA without stenting (POBA group: control) were analyzed. After 1 year, the stent group had a lower incidence of the combined clinical endpoint (death, rehospitalization due to congestive heart failure, nonfatal myocardial infarction, repeat angioplasty, CABG, or cerebrovascular events) compared to the POBA group (17.1% versus 39.0%, P = 0.049). After 5 years, the incidences of congestive heart failure and cardiac death were the same in both groups. However, compared to the POBA group, the stent group had a lower combined clinical endpoint (34.1% versus 61.0%, P = 0.027). The Kaplan-Meier event-free survival curves of the stent group showed a significantly lower occurrence of clinical events compared to the POBA group (P = 0.0116). Multiple logistic regression analysis of clinical events identified age > or = 69 years (P = 0.0092, odds ratio = 4.179) and stenting (P = 0.0158, odds ratio = 0.279) as explanatory factors. Compared with POBA, primary stenting for acute myocardial infarction results in a better long-term clinical outcome.

Identification of viral genomic elements responsible for rabies virus neuroinvasiveness.

Attenuated tissue culture-adapted and natural street rabies virus (RV) strains differ greatly in their neuroinvasiveness. To identify the elements responsible for the ability of an RV to enter the CNS from a peripheral site and to cause lethal neurological disease, we constructed a full-length cDNA clone of silver-haired bat-associated RV (SHBRV) strain 18 and exchanged the genes encoding RV proteins and genomic sequences of this highly neuroinvasive RV strain with those of a highly attenuated nonneuroinvasive RV vaccine strain (SN0). Analysis of the recombinant RV (SB0), which was recovered from SHBRV-18 cDNA, indicated that this RV is phenotypically indistinguishable from WT SHBRV-18. Characterization of the chimeric viruses revealed that in addition to the RV glycoprotein, which plays a predominant role in the ability of an RV to invade the CNS from a peripheral site, viral elements such as the trailer sequence, the RV polymerase, and the pseudogene contribute to RV neuroinvasiveness. Analyses also revealed that neuroinvasiveness of an RV correlates inversely with the time necessary for internalization of RV virions and with the capacity of the virus to grow in neuroblastoma cells.

Incremental prognostic implications of brain natriuretic peptide, cardiac sympathetic nerve innervation, and noncardiac disorders in patients with heart failure.

UNLABELLED: Plasma brain natriuretic peptide (BNP) level and cardiac autonomic function are closely related to prognosis in patients with heart failure. However, their correlation and incremental prognostic values in human heart failure are unclear. We sought to evaluate the correlation between BNP level and cardiac sympathetic innervation assessed by (123)I-metaiodobenzylguanidine ((123)I-MIBG) and the prognostic value of combined assessment of risk factors for mortality in patients with heart failure. METHODS: After conventional examinations and measurements of plasma BNP level and heart-to-mediastinum ratio (HMR) of cardiac (123)I-MIBG activity, 158 patients with heart failure were prospectively followed with an endpoint of cardiac death for 16 mo. RESULTS: Fifteen deaths due to pump failure and 2 sudden cardiac deaths were documented. Plasma BNP level correlated with HMR significantly but not so tightly (r = 0.330, P < 0.0001). Univariate analysis identified plasma BNP level, HMR, chronic renal dysfunction, diabetes mellitus, age, and use of nitrates as significant predictors of fatal pump failure, and multivariate Cox analysis showed that plasma BNP level was the most powerful predictor of cardiac death. Patients with both plasma BNP level of > or = 172 pg/mL and late HMR of < or =1.74 had a greater annual rate of fatal pump failure than did those without (17.5%/y vs. 0%-3.9%/y, respectively). The hazard ratio of plasma BNP level (7.2) or cardiac (123)I-MIBG activity (10.1) increased to 34.4 when both variables were used, and prevalence of fatal pump failure significantly increased from 22% to 62.5% when diabetes mellitus and chronic renal dysfunction were present with a higher plasma BNP level and low cardiac (123)I-MIBG activity. CONCLUSION: Plasma BNP level is a stronger predictor than other risk factors for mortality in heart failure patients and is statistically significantly, but roughly, related to cardiac sympathetic nerve innervation. Impaired cardiac sympathetic nerve innervation and the presence of diabetes mellitus and chronic renal dysfunction, however, improve risk stratification of patients with heart failure and increased plasma BNP concentration.