18F-FDG PET imaging of myocardial viability in an experienced center with access to 18F-FDG and integration with clinical management teams: the Ottawa-FIVE substudy of the PARR 2 trial.
National Cardiac PET Centre and Division of Cardiology, Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
(18)F-FDG PET may assist decision making in ischemic cardiomyopathy. The PET and Recovery Following Revascularization (PARR 2) trial demonstrated a trend toward beneficial outcomes with PET-assisted management. The substudy of PARR 2 that we call Ottawa-FIVE, described here, was a post hoc analysis to determine the benefit of PET in a center with experience, ready access to (18)F-FDG, and integration with clinical teams.
Included were patients with left ventricular dysfunction and suspected coronary artery disease being considered for revascularization. The patients had been randomized in PARR 2 to PET-assisted management (group 1) or standard care (group 2) and had been enrolled in Ottawa after August 1, 2002 (the date that on-site (18)F-FDG was initiated) (n = 111). The primary outcome was the composite endpoint of cardiac death, myocardial infarction, or cardiac rehospitalization within 1 y. Data were compared with the rest of PARR 2 (PET-assisted management [group 3] or standard care [group 4]).
In the Ottawa-FIVE subgroup of PARR 2, the cumulative proportion of patients experiencing the composite event was 19% (group 1), versus 41% (group 2). Multivariable Cox proportional hazards regression showed a benefit for the PET-assisted strategy (hazard ratio, 0.34; 95% confidence interval, 0.16-0.72; P = 0.005). Compared with other patients in PARR 2, Ottawa-FIVE patients had a lower ejection fraction (25% +/- 7% vs. 27% +/- 8%, P = 0.04), were more often female (24% vs. 13%, P = 0.006), tended to be older (64 +/- 10 y vs. 62 +/- 10 y, P = 0.07), and had less previous coronary artery bypass grafting (13% vs. 21%, P = 0.07). For patients in the rest of PARR 2, there was no significant difference in events between groups 3 and 4. The observed effect of (18)F-FDG PET-assisted management in the 4 groups in the context of adjusted survival curves demonstrated a significant interaction (P = 0.016). Comparisons of the 2 arms in Ottawa-FIVE to the 2 arms in the rest of PARR 2 demonstrated a trend toward significance (standard care, P = 0.145; PET-assisted management, P = 0.057).
In this post hoc group analysis, a significant reduction in cardiac events was observed in patients with (18)F-FDG PET-assisted management, compared with patients who received standard care. The results suggest that outcome may be benefited using (18)F-FDG PET in an experienced center with ready access to (18)F-FDG and integration with imaging, heart failure, and revascularization teams.
Preliminary intravenous injection of cannabinoid receptor agonist HU-210 (0.05 mg/kg) reduced the incidence of ventricular arrhythmias during 10-min coronary occlusion and 10-min reperfusion in chloralose-anesthetized rats. Preliminary injection of type I cannabinoid receptor antagonist SR 141716A (3 mg/kg) had no effect on the antiarrhythmic effect of HU-210, while type II cannabinoid receptor antagonist SR 144528 (1 mg/kg) completely abolished the effect of HU-210. Preconditioning with glibenclamide (0.3 mg/kg), an inhibitor of ATP-dependent K(+)-channels, did not affect the antiarrhythmic activity of HU-210. These findings suggest that antiarrhythmic effect of HU-210 is mediated through activation of type II cannabinoid receptors rather than activation of K(+)-channels.
To assess lung function, gas exchange, exercise capacity, and right-sided heart hemodynamics, including pulmonary artery pressure, in patients long term after pneumonectomy.
Among 523 consecutive patients who underwent pneumonectomy for lung cancer between January 1992 and September 2001, 117 were alive in 2006 and 100 were included in the study. During a 1-day period, each patient had complete medical history, chest radiographs, pulmonary function studies, resting arterial blood gas analysis, 6-minute walk test, and Doppler echocardiography.
Most patients (N = 73) had no or only minimal dyspnea. On the basis of predicted values, functional losses in forced expiratory volume in 1 second and forced vital capacity were 38% ± 18% and 31% ± 24%, respectively, and carbon monoxide diffusing capacity decreased by 31% ± 18%. There was a significant correlation between preoperative and postoperative forced expiratory volume in 1 second (P
Aging is associated with left ventricular hypertrophy, dilatation, and fibrosis of the heart. The Fischer 344/Brown Norway F1 (F344/BNF1) rat is recommended for age-related studies by the National Institutes on Aging because this hybrid rat lives longer and has a lower rate of pathological conditions than inbred rats. However, little is known about age-associated changes in cardiac and aortic function and structure in this model. This study evaluated age-related cardiac changes in male F344/BNF1 rats using ECHO, gross, and microscopic examinations. Rats aged 6-, 30-, and 36-mo were anesthetized and two-dimensional ECHO measurements, two-dimensional guided M-mode, Doppler M-mode, and other recordings from parasternal long- and short-axis views were obtained using a Phillips 5500 ECHO system with a 12 megahertz transducer. Hearts and aortas from sacrificed rats were evaluated grossly and microscopically. The ECHO studies revealed persistent cardiac arrhythmias (chiefly PVCs) in 72% (13/18) of 36-mo rats, 10% (1/10) of 30-mo rats, and none in 6-mo rats (0/16). Gross and microscopic studies showed left ventricular (LV) dilatation, borderline to mild hypertrophy, and areas of fibrosis that were common in 36-mo rats, less evident in 30-mo rats, and absent in 6-mo rats. Aging was associated with mild to moderate decreases of LV diastolic and systolic function. Thus, male F344/BN F1 rats demonstrated progressive age-related (a) decline in cardiac function (diastolic and systolic indices), (b) LV structural changes (chamber dimensions, volumes, and wall thicknesses), and (c) persistent arrhythmias. These changes are consistent with those in humans. The noninvasive ECHO technique offers a means to monitor serial age-related cardiac failure and therapeutic responses in the same rats over designated time intervals.
Aged rat myocardium exhibits normal adenosine receptor-mediated bradycardia and coronary vasodilation but increased adenosine agonist-mediated cardioprotection.
The purpose of this study was to determine whether aged myocardium exhibits decreased responsiveness to adenosine A1 and A(2a) receptor activation. Studies were conducted in adult (4-6 months) and aged (24-26 months) Fischer 344 x Brown Norway hybrid (F344 x BN) rats. Effects of the adenosine A1/A(2a) agonist AMP579 were measured in isolated hearts and in rats submitted to in vivo regional myocardial ischemia. Aged isolated hearts exhibited lower spontaneous heart rates and higher coronary resistance, as well as normal A1- and A(2a)-mediated responses. There was no difference in control infarct size between adult and aged rats; however, AMP579 treatment resulted in a 50% greater infarct size reduction in aged rats (18 +/- 4% of risk area) compared to adult rats (37 +/- 3%). These findings suggest that adenosine A1 and A(2a) receptor-mediated effects are not diminished in normal aged myocardium, and that aged hearts exhibit increased adenosine agonist-induced infarct reduction.
We report the influence of aging on multiple markers of oxidative-nitrosative stress in the heart of adult (6-month), aged (30-month) and very aged (36-month) Fischer 344/NNiaHSd x Brown Norway/BiNia (F344/NXBN) rats. Compared to adult (6-month) hearts, indices of oxidative (superoxide anion [O2*-], 4-hydroxy-2-nonenal [4-HNE]) and nitrosative (protein nitrotyrosylation) stress were 34.1 +/- 28.1%, 186 +/- 28.1% and 94 +/- 5.8% higher, respectively, in 36-month hearts and these findings were highly correlated with increases in left ventricular wall thickness (r > 0.669; r > 0.710 and P
Over a 12-year period, from 1970 to 1981, 30 600 babies were born at the Department of Obstetrics and Gynecology, University Central Hospital, Turku, Finland. During that period, the use of electronic fetal monitoring increased remarkably, being involved in 9, 12, 33 and 95% of all vaginal deliveries during four consecutive 3-year periods. The number of intrapartum deaths during the same 12-year period was 52, giving an overall rate of 1.7 per thousand. When 15 lethally malformed infants are excluded, the rate becomes 1.2 per thousand. In the four consecutive 3-year periods, the death rates were 1.7, 1.9, 1.0 and 0.3 per thousand. Electronic fetal monitoring was not undertaken in any of the cases leading to fetal death. The main factor leading to fetal death could be considered to be hypoxia in approximately 90% of the deaths of normally formed babies. The most common reasons for hypoxia were placental abruption and cord entanglement, yet in many cases only the decreased placental perfusion could be suggested to have caused the hypoxia. The mean weight of those babies that died intrapartally decreased significantly, being approximately 1 250 g during the last 3-year period.
Familial amyloidosis, Finnish type (FAF), is a gelsolin-related inherited systemic amyloidosis. We report autonomic nervous system and cardiac findings in a study of 30 FAF patients (18 females, 12 males aged 27-74 years; mean 53.9 years). Cardiovascular reflex tests showed a significant decrease in heart rate variation in FAF patients compared with healthy controls. Orthostatic hypotension was found in 9 of 28 FAF patients, but only in 3 of 69 controls. Signs of amyloid cardiopathy were rare at clinical examination and in radio-, echocardio- and electrocardiographic examinations. Histological and immunohistochemical studies revealed amyloid deposition and immunoreactivity against the gelsolin-related FAF amyloid subunit in autonomic nervous system structures and in cardiac tissue in 3 autopsied FAF patients. The results show that minor autonomic nervous system dysfunction can be found in FAF, while clinically significant amyloid cardiopathy or autonomic neuropathy is not characteristic of this type of amyloidosis.
