Coronary artery bypass graft surgery and primary percutaneous coronary intervention choices in patients with similar coronary anatomy: A computer-based simulation examines the sex gap.

BACKGROUND: Sex differences (or a 'sex gap') exist in the rates of cardiac revascularization. It was evaluated whether physician preference contributes to this difference. OBJECTIVES: To obtain information on how cardiac specialists manage male and female patients being evaluated for coronary artery disease. METHODS: A computer-based patient simulation program was developed. Six sex-matched clinical vignettes (three pairs) with uninterpreted coronary angiograms were shown to specialists, who were blinded to the purpose of the study. The sex-matched scenarios were balanced with respect to symptoms, comorbidities and coronary anatomy. Physicians were surveyed on management and rationale. RESULTS: Fifty physicians were surveyed, consisting mainly of cardiologists from tertiary cardiac centres in Ontario. Among the three sexmatched pairs, the frequencies at which percutaneous coronary intervention (including drug-eluting stents), bypass surgery and medical therapy were chosen did not differ across sexes. The means for men and women, respectively, were 47% and 50% for percutaneous coronary intervention, 32% and 26% for bypass surgery, and 21% and 24% for medical treatment. CONCLUSIONS: In the present pilot study, cardiac specialists chose similar rates of medical, interventional and surgical procedures independent of a patient's sex. Although large registry trials show that sex differences in management exist, the present data suggest that cardiac specialist preference is less likely to be a factor if coronary angiography was performed. Further research is required to explore the causes of sex discrepancies in cardiac care.

Atrial natriuretic peptide augments the variability of sympathetic nerve activity in human heart failure.

OBJECTIVES: Activation of the sympathetic nervous system, decreased heart rate variability (HRV), and loss of modulation of muscle sympathetic nerve activity (MSNA) within the low frequency (LF, 0.05-0.15 Hz) range are three adverse features of advanced congestive heart failure (CHF). In healthy men, atrial natriuretic peptide (ANP) infusion attenuates reflex increases in MSNA and reduces LF components of HRV spectral power. Sympathoinhibitory actions have also been documented in CHF, but effects on the variability of MSNA and HRV have not been described. DESIGN AND METHODS: Heart rate and MSNA were recorded in 10 men (aged 39 +/- 3 years, mean +/- SE) with dilated cardiomyopathy (mean EF 20 +/- 4%) treated with angiotensin converting enzyme (ACE) inhibitors. Subjects received i.v. ANP (50 microg bolus then 50 ng/kg/min) and nitroglycerin (NTG, 8 mg/min) as a hemodynamic control. Signals at baseline, and 13-20 min into each infusion were submitted to spectral analysis. RESULTS: ANP had no effect on HRV, but increased MSNA LF (from 7.9 +/- 1.5 to 12.1 +/- 2.6 U2; P< 0.02) and total spectral power (from 47.9 +/- 5.4 to 61.9 +/- 6.8 U2; P < 0.05). NTG had no effect on the variability of MSNA or HRV. CONCLUSIONS: In CHF patients receiving ACE inhibitors, ANP (i) does not suppress HRV and (ii) enhances the modulation of MSNA, particularly within the LF range. This latter action is not observed with NTG. These findings suggest beneficial actions of exogenous ANP on neurogenic circulatory control.

Stress perfusion/metabolism imaging: a pilot study for a potential new approach to the diagnosis of coronary disease in women.

BACKGROUND: The diagnosis of coronary artery disease (CAD) in women continues to be a challenge. F-18 deoxyglucose (FDG) positron emission tomography (PET) has been used for detection of myocardial ischemia at rest. Little has been reported about FDG stress imaging. The aim of this pilot study was to assess stress FDG PET imaging for defining CAD in a group of women referred for chest pain. METHODS: Stress FDG imaging was performed in 19 women (mean age 59 +/- 10 years). All had abnormal stress testing before entering the study. FDG and 2-methoxy-2-methylpropyl isonitrile were injected at peak stress (treadmill n = 8, dipyridamole n = 11) followed by PET and single photon emission computed tomography image acquisitions. Myocardial ischemia was defined by regions that demonstrated both a defect on perfusion imaging and increased FDG uptake relative to uptake in normal perfusion zones. Defect/normal zone FDG ratios were also determined. Coronary angiography was performed on all patients. RESULTS: Average, or mean, body mass index was high at 29.2 +/- 5 kg/m2. Nine of 19 patients had significant CAD. Eight of 9 with CAD had FDG-defined ischemia. Nine of the 10 without CAD had negative FDG images (sensitivity 89%, specificity 90%). The average defect/normal zone FDG ratio was greater in patients with CAD than in those without (2.4 +/- 1.9 vs 0.9 +/- 0.4, P < .05). CONCLUSIONS: Regional FDG uptake in areas of perfusion defects with stress increased in this group with CAD. These pilot data suggest that stress FDG PET may be diagnostically helpful in obese female patients. This novel approach may complement current methods of CAD detection in women and warrants further study.

Use of hormone replacement therapy among cardiac patients at a Canadian academic centre.

BACKGROUND: Although hormone replacement therapy (HRT) is associated with a reduced risk of coronary artery disease (CAD), use of this treatment among post-menopausal women is not widespread. The authors sought to determine the extent of HRT use in a select population of women at high risk for CAD. METHODS: A cross-sectional survey was performed involving all consecutive post-menopausal women who attended a cardiology clinic in a Toronto teaching hospital between January 1996 and August 1997. A chart review was followed by a telephone interview with the patients or their physicians. The utilization rate of HRT was obtained. Predictors of HRT use were identified using a multivariate logistic regression model. RESULTS: A total of 80 women with risk factors for CAD, symptoms suspicious of CAD or definite CAD diagnosed after cardiac investigations were included in the survey. Information on HRT use or nonuse was documented in 17 (21%) of the charts. Of the 72 women for whom data on HRT were available 16 (22%) were currently using it, 41 (57%) were not, and 15 (21%) had used it in the past. Five women (7%) were receiving HRT but there was no chart documentation. On multivariate analysis, younger women were more likely than older women to use HRT (odds ratio 0.91, 95% confidence interval 0.22-0.96; p < 0.05). Coronary risk profile, CAD diagnosis and history of hysterectomy were not associated with HRT use. Of the 41 women who had never received HRT 10 (24%) had possible contraindications (e.g., breast cancer or deep vein thrombosis); the proportion was similar in the group of women who were current or past users of HRT (29%). INTERPRETATION: Documentation of HRT use in patient charts is lacking. Few women in the study who were at risk for CAD were currently using HRT. The data support the need for better adherence to optimal practices in the management of women at high risk for CAD.

Effect of atrial natriuretic peptide on muscle sympathetic activity and its reflex control in human heart failure.

BACKGROUND: The purpose of this study was to determine if atrial natriuretic peptide (ANP) exerts a relative inhibitory effect on muscle sympathetic nerve activity (MSNA) at rest and during nonhypotensive lower body negative pressure (LBNP) in heart failure, as in healthy subjects. METHODS AND RESULTS: Fifteen men (age 39+/-2 years [mean+/-SE]) with dilated cardiomyopathy (ejection fraction 18+/-3%) received intravenous ANP (50 microgram bolus, then 50 ng. kg-1. min-1) and nitroglycerin (NTG, 8 mg/min) as a hemodynamic control. During each infusion MSNA, blood pressure (BP), central venous pressure (CVP), and heart rate (HR) were recorded before and during LBNP at -6 and -12 mm Hg. NTG and ANP caused similar and significant reductions in CVP and diastolic BP, but resting MSNA did not increase with either infusion. LBNP at -6 mm Hg lowered CVP (P<0.05), whereas LBNP at -12 mm Hg caused significant reductions in CVP, systolic BP, and diastolic BP. These effects of nonhypotensive and hypotensive LBNP on CVP and BP were similar during ANP and NTG infusions, yet MSNA was lower both before and with LBNP during ANP (P<0.02). Nonhypotensive LBNP increased MSNA during NTG (+133+/-68 Units; P<0.001) but not during ANP infusion (+24+/-23 Units; P=NS). CONCLUSIONS: These observations are consistent with the concept that ANP exerts a sympathoinhibitory action in heart failure. This is most evident in response to reductions in atrial pressures that do not affect systemic BP.

Angiotensin AT1 receptor blockade abolishes the reflex sympatho-excitatory response to adenosine.

We tested the hypothesis that endogenous angiotensin II participates in the direct and reflex effects of adenosine on the sympathetic nervous system. Nine healthy men were studied after 1 wk of the angiotensin II type I receptor antagonist losartan (100 mg daily) or placebo, according to a double-blind randomized crossover design. Bilateral forearm blood flows, NE appearance rates, and total body NE spillover were determined before and during graded brachial arterial infusion of adenosine (0.5, 1.5, 5, and 15 microg/100 ml forearm tissue) and nitroprusside. Adenosine increased total body NE spillover (P < 0.05) whereas nitroprusside did not. Losartan lowered BP (P < 0.05), had no effect on total body NE spillover at rest, or forearm vasodilation during either infusion, but reduced the systemic noradrenergic response to adenosine from 1.0+/-0.4 nmol/min on the placebo day to 0.2+/-0.3 nmol/min (P < 0.01), and forearm NE appearance rate in response to adenosine was lower in the infused, as compared with the contralateral arm (P = 0.04). The sympatho-excitatory reflex elicited by adenosine is mediated through pathways involving the angiotensin II type I receptor. Interactions between adenosine and angiotensin II may assume importance during ischemia or congestive heart failure and could contribute to the benefit of converting enzyme inhibition in these conditions.

Neural and hypotensive effects of angiotensin II receptor blockade.

Angiotensin II participates in the neural regulation of the heart and circulation at both central and peripheral sites. To explore the role of endogenous angiotensin II in blood pressure regulation, we conducted a randomized double-blind crossover trial in nine young healthy men (aged 33+/-3 [mean+/-SE] years) studied in the absence of salt restriction, comparing the effect of 1 week treatment with the angiotensin II receptor antagonist losartan (100 mg daily) against placebo with respect to the following variables, recorded during supine rest: intra-arterial blood pressure (BP), heart rate (HR), forearm vascular resistance and norepinephrine appearance rate, total body norepinephrine spillover, variability of BP and HR (spectral analysis), and baroreflex sensitivity for HR (gain of the transfer function from systolic BP to HR). Blood pressure was 119+/-7/66+/-4 mm Hg (systolic BP/diastolic BP) after 1 week of placebo and 112+/-6/61+/-3 mm Hg after 1 week of losartan (P<.05). Forearm vascular resistance tended to fall, from 42.3+/-6.9 U on placebo to 32.8+/-5.0 U with losartan treatment (P=.07). Losartan had no effect on HR (60+/-3 on placebo versus 59+/-2 beats per minute with losartan), total body norepinephrine spillover (3.0+/-0.8 versus 3.3+/-1.2 nmol/min), forearm norepinephrine appearance rate (3.8+/-1.1 versus 5.3+/-1.1 pmol/100 mL forearm tissue per minute), power in the high- or low-frequency components of the HR variability and BP variability spectra or on baroreflex sensitivity for HR. Endogenous angiotensin II contributes to the maintenance of supine BP in normal subjects, studied in the absence of sodium restriction. The fall in BP caused by losartan is accompanied by a resetting of the baroreflex regulation of HR and sympathetic outflow, but baroreflex sensitivity for heart rate is not altered. Therefore, the reduction in BP observed after short-term angiotensin type 1 receptor antagonism may be achieved through a direct effect on vascular tone rather than through a primary reduction in sympathetic outflow.