Circadian Variation of Cardiac Performance in Coronary Heart Disease

To study the circadian variation of cardiac performance in patients with coronary heart disease, three exercise tests on a bicycle crgometer were performed during the active part of the day (10 a.m., 2 p.m. and 6 p.m.), recording ST-segment depression and pulmonary capillary wedge pressure. Ten male patients with angiographically documented coronary heart disease underwent bicycle ergometry during placebo and during nitrate therapy (placebo controlled, double-blind crossover 2 × 20 mg IS-5-MN and 1 × 120 mg ISDN sustained release). During placebo as well as during nitrate therapy there was a gradual decrease of cardiac performance during the day, documented by the increase in ST-depression and pulmonary capillary wedge pressure at equal work loads. High nitrate concns led to a significant reduction of both ST-depression and preload with a marked circadian-phase dependency of cardiovascular effects.     

Chronotherapy in Coronary Heart Disease: Comparison of Two Nitrate Treatments

The purpose of this study was to assess the ischemic burden and the hemodynamic changes during daily activities in patients with coronary heart disease. Three exercise tests were performed during the day (10:00 a.m., 2:00 p.m., 6:00 p.m.), recording ST-segment depression, pulmonary artery pressure, pulmonary wedge pressure, and cardiac output as well as heart rate and systemic blood pressure during placebo and nitrate therapy. With placebo as well as nitrate therapy there was a gradual increase of ischemia and preload and a decrease of cardiac output during the day. High nitrate concentrations led to a significant reduction of both preload and ST depression with a marked circadian phase dependency of cardiovascular effects.     

Chronotherapy in Coronary Heart Disease: Comparison of Two Nitrate Treatments

The purpose of this study was to assess the ischemic burden and the hemodynamic changes during daily activities in patients with coronary heart disease. Three exercise tests were performed during the day (10:00 a.m., 2:00 p.m., 6:00 p.m.), recording ST-segment depression, pulmonary artery pressure, pulmonary wedge pressure, and cardiac output as well as heart rate and systemic blood pressure during placebo and nitrate therapy. With placebo as well as nitrate therapy there was a gradual increase of ischemia and preload and a decrease of cardiac output during the day. High nitrate concentrations led to a significant reduction of both preload and ST depression with a marked circadian phase dependency of cardiovascular effects.     

Effects of pneumatic antishock garment inflation in normovolemic subjects

This study examines the effects of inflation of pneumatic antishock garments (PASG) in 10 normovolemic men (mean age 44 +/- 6 yr) undergoing diagnostic catheterization. Seven subjects had normal heart function and no evidence of coronary artery disease (CAD); three patients had CAD. High-fidelity multisensor catheters were employed to simultaneously record right and left heart pressures before PASG inflation and after inflation to 40, 70, and 100 mmHg. A thermal dilution catheter was used to obtain pulmonary capillary wedge pressure and cardiac output. Counterpressure increases greater than or equal to 40 mmHg were associated with significant changes in left and right heart pressures. Right and left ventricular end-diastolic pressures increased 100% (P less than 0.01); mean pulmonary arterial and aortic pressures increased 77 and 25%, respectively (P less than 0.01); systemic vascular resistance increased 22% (P less than 0.05) and pulmonary vascular resistance did not change in normal subjects at maximum PASG inflation. Heart rate, cardiac output, and aortic and pulmonary arterial pulse pressures did not change during inflation in either group. Right and left ventricular end-diastolic pressures and pulmonary capillary wedge pressure were greater (P less than 0.05) in the CAD group compared with the normal subjects during PASG inflation. The data suggest that the primary mechanism whereby PASG inflation induces changes in central hemodynamics in normovolemic subjects is through an acute increase in left ventricular afterload. PASG changes in afterload and pulmonary capillary wedge pressure imply that these devices should be used with caution in patients with compromised cardiac function.     

Coenzyme Q10 treatment in serious heart failure.

Several noninvasive studies have shown the effect on heart failure of treatment with coenzyme Q10. In order to confirm this by invasive methods we studied 22 patients with mean left ventricular (LV) ejection fraction 26%, mean LV internal diameter 71 mm and in NYHA class 2-3. The patients received coenzyme Q10 100 mg twice daily or placebo for 12 weeks in a randomized double-blinded placebo controlled investigation. Before and after the treatment period, a right heart catheterisation was done including a 3 minute exercise test. The stroke index at rest and work improved significantly, the pulmonary artery pressure at rest and work decreased (significantly at rest), and the pulmonary capillary wedge pressure at rest and work decreased (significantly at 1 min work). These results suggest improvement in LV performance. Patients with congestive heart failure may thus benefit from adjunctive treatment with coenzyme Q10.     

Cardiovascular effects of intravenous and intracoronary administration of atrial natriuretic peptide in halothane anesthetized dogs

Cardiovascular actions of synthetic 1-28 human natriuretic peptides (hANP) were examined in dogs anesthetized with halothane. In seven closed-chest dogs a Swan-Ganz catheter was inserted for measurement of cardiac output. Intravenous infusion of increasing doses of hANP (0.1, 0.3, 0.9 microgram/kg/min) lowered mean aortic pressure without affecting heart rate significantly. Cardiac output and pulmonary wedge pressure were markedly decreased while total peripheral resistance was increased significantly. All these parameters returned to control levels after 1 hr of recovery with an 100-150ml of saline infusion to increase pulmonary capillary wedge pressure to the preinfusion value. Intracoronary infusion of hANP (0.05 and 0.1 microgram/kg/min) did not cause any significant changes in coronary flow and regional contraction. These results indicate that the hypotensive action of hANP is due to a decrease in cardiac output mediated by reduced preload but not by negative inotropic action.     

Flosequinan in heart failure: acute haemodynamic and longer term symptomatic effects.

There is no single, simple test with which to evaluate new treatments for heart failure. Various methods need to be used, and a study of both the acute haemodynamic and longer term symptomatic effects of flosequinan, a new direct acting arteriolar and venous vasodilator, was therefore carried out in patients with heart failure. In one group of patients flosequinan increased cardiac output and caused a fall in pulmonary capillary wedge pressure, both effects lasting for 24 hours. In a double blind, placebo controlled study in another group flosequinan improved mean exercise tolerance from 9.9 to 12.7 minutes after four weeks of treatment. The drug also reduced perceived exertion during submaximal exercise and increased calf and therefore skeletal muscle blood flow. It reduced plasma renin activity and noradrenaline concentrations. Flosequinan possesses all the important properties of a drug likely to be of value in the treatment of heart failure.     

Increased pulmonary vascular capacitance with beta-adrenergic receptor stimulation: an experimental study of the effect of isoproterenol on the pulmonary vascular volume-pressure relationship

The present study is an investigation of the effect of beta-adrenergic receptor stimulation by isoproterenol on pulmonary vascular capacitance. The experiments were done in six intact-chest, anaesthetized dogs in which pulmonary and cardiac blood volumes were assessed by blood pool scintigraphy. Isoproterenol (0.150 microgram.kg-1.min-1) significantly (p less than 0.005) lowered pulmonary capillary wedge pressure (PPCW) and pulmonary artery pressure (PPA) but did not significantly change pulmonary blood volume (PBV). Left ventricular end-diastolic pressure and total cardiac volume both significantly (p less than 0.005) decreased. Pulmonary vascular volume-pressure (V-P) relationships before and during isoproterenol were described by means of blood transfusions and hemorrhage. In individual dogs the PBV-PPCW and the PBV-(PPCW + PPA)/2 relationships were significantly shifted upward by isoproterenol (p less than 0.05 or less); slope changes were variable. Pooled data from all dogs also showed a significant (p less than 0.001) upward shift in the pulmonary vascular V-P relationship regardless of which measure of distending pressure was used. These results suggest that beta-receptor stimulation by isoproterenol increases pulmonary vascular capacitance by increasing the unstressed volume.     

The relationship between urotensin II plasma immunoreactivity and left ventricular filling pressures in coronary artery disease

The role of urotensin II (U-II)--a vasoactive, mitogenic, and inotropic, peptide--in the pathophysiology of heart failure is controversial. The present study explores the relationship between plasma U-II immunoreactivity (U-IIIR) and hemodynamics in patients with coronary artery disease (CAD). Thirty-six patients with CAD-3 undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) and 36 medical patients (MED group) with CAD-1 to CAD-3 during right heart catheterization were studied. Significant correlations were observed between pulmonary capillary wedge pressure (PCWP) and U-IIIR--determined by enzyme immunoassay (EIA)--before (rho = 0.83) and after (rho = 0.6) cardiopulmonary bypass in the CABG group. With the exception of the CPB period, CABG patients with increased PCWP before CPB had higher U-II(IR) concentrations throughout the procedure. Significant correlations were observed between U-IIIR, proANP, proBNP, and mean right ventricular pressure (RVPM) in MED patients. No correlation was detectable between U-IIIR and PCWP. However, MED patients with CAD-3 (n = 13) had higher levels of U-IIIR, NTproANPIR (RIA), NTproBNPIR (EIA) and higher cardiac filling pressures than patients with CAD-1 (n = 13). These findings support an association between plasma U-IIIR levels and diastolic myocardial dysfunction in ischemic heart failure. The discrepancies regarding left and right cardiac filling pressures and U-IIIR levels in CABG and MED patients require further evaluation.     

Effects of digoxin on chemoreflex in patients with chronic heart failure.

The effects of digitalis on the baroreflexes in human chronic heart failure have been well studied. Similarly, since it has been recently shown that chemoregulation remains generally effective during cardiac failure, the goal of this study was to evaluate the effects of a chronic administration of digoxin on the chemoreflexes. Hemodynamic and blood gas parameters were assessed in 7 patients with chronic congestive heart failure before and after chronic administration for 10 days of digoxin therapy (0.25 mg daily). In both situations measurements were performed 1/ in baseline conditions at room air and, 2/ after inhalation of pure O2 for 30 min, in order to inhibit the activation of the chemoreflexes. At room air, acute O2 inhalation resulted in a significant decrease in heart rate and cardiac output. After digoxin therapy, comparatively to pre-treatment values, cardiac output, stroke volume and PaO2 were significantly higher while heart rate, systemic resistance and pulmonary wedge pressure were lower. Furthermore, acute O2 inhalation did not modify heart rate or any hemodynamic variables. These results suggest that after digoxin therapy chemoreflex was no more activated in these patients. This effect may be related to the sympatho-inhibitory and to the positive inotropic effects of digoxin: improving hemodynamic and blood gas parameters may result in the inactivation of the reflex.     

Haemodynamic patterns in ST-elevation myocardial infarction: incidence and correlates of elevated filling pressures

Objectives. We sought to study the incidence and clinical correlates of elevated filling pressures in ST-elevation myocardial infarction (STEMI) patients, without physical signs of heart failure and treated with primary coronary angioplasty. Background. Haemodynamic data, as measured with a Swan-Ganz catheter, are not routinely obtained in STEMI patients. At admission, low blood pressure, increased heart rate, sweating, increased respiration rate, rales, oedema, and a third heart sound are indicative of heart failure. Methods. All consecutive STEMI patients were monitored by a Swan-Ganz catheter and central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure (PAS) and cardiac index (CI) were measured. To investigate the clinical correlates of the haemodynamic status patients were classified according to previously defined haemodynamic criteria. Results. We studied 90 patients, aged 60.5±13.1 year, 76% were male. Mortality at 30 days was 2/90 (2.2%). Patients with impaired haemodynamics presented later and had larger myocardial infarct sizes. CVP, PCWP and PAS were above normal in 36 (40%) patients. Conclusion. A large proportion of STEMI patients without physical signs of heart failure have elevation of right- as well as left-sided cardiac filling pressures. (Neth Heart J 2007:15:95-9.)     

Alternative hormone replacement regimens: is there a need for further clinical trials?

PURPOSE OF REVIEW: To review the randomized trials of hormone replacement therapy. RECENT FINDINGS: Studies have shown that conjugated equine estrogen 0.625 mg a day plus medroxyprogesterone acetate 2.5 mg a day increased the risk of cardiovascular events during the first year of treatment in women both with and without coronary heart disease. Conjugated equine estrogen plus medroxyprogesterone acetate also increased the overall risk of myocardial infarction and stroke in women without coronary heart disease, and myocardial infarction or death in women with coronary heart disease, and also increased the risk of breast cancer, cognitive decline and dementia. Unopposed, oral 17B-estradiol increased the risk of stroke during the first 6 months of treatment in women with a previous stroke. Oral 17B-estradiol with or without cyclic progestin had no effect on the progression of atherosclerosis or reinfarction. Transdermal 17B-estradiol plus cyclic progestin was associated with a non-significant increase in coronary heart disease events in women with coronary heart disease. Compared with placebo, cardiovascular events increased in the ongoing estrogen-only arm of the Women's Health Initiative, indicating that unopposed conjugated equine estrogen is unlikely to be cardioprotective. However, oral 17B-estradiol retarded the progression of subclinical atherosclerosis in younger women without coronary heart disease. SUMMARY: Hormone replacement therapy should not be initiated for the primary or secondary prevention of coronary heart disease in women. A trial of 17B-estradiol started at menopause in women without coronary heart disease should be considered.     

Bradykinin actively modulates pulmonary vascular pressure-cardiac index relationships

Our objectives were to investigate the pulmonary vascular effects of exogenously administered bradykinin at normal and reduced levels of cardiac index in intact conscious dogs and to assess the extent to which the pulmonary vascular response to bradykinin is the result of either cyclooxygenase pathway activation or reflex activation of sympathetic beta-adrenergic and -cholinergic receptors. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by step-wise constriction of the thoracic inferior vena cava to reduce Q. In intact dogs, bradykinin (2 micrograms X kg-1 X min-1 iv) caused systemic vasodilation, i.e., systemic arterial pressure was slightly decreased (P less than 0.05), Q was markedly increased (P less than 0.01), and mixed venous PO2 and oxygen saturation (SO2) were increased (P less than 0.01). Bradykinin decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) over the entire range of Q studied (140-60 ml X min-1 X kg-1) in intact dogs. During cyclooxygenase pathway inhibition with indomethacin, bradykinin again decreased (P less than 0.05) pulmonary arterial pressure-pulmonary capillary wedge pressure at every level of Q, although the magnitude of the vasodilator response was diminished at lower levels of Q (60 ml X min-1 X kg-1). Following combined administration of sympathetic beta-adrenergic and -cholinergic receptor antagonists, bradykinin still decreased (P less than 0.01) pulmonary arterial pressure-pulmonary capillary wedge pressure over the range of Q from 160 to 60 ml X min-1 X kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary circulation and right ventricular function in primary arterial hypertension]

Selected parameters of the pulmonary circulation and right ventricular performance were studied in 30 patients with primary arterial hypertension. Four patients belonged to the WHO class I, four to class I/II, 18 to class II and the remaining four to class III. Patients were eligible, if they were in sinus rhythm, without symptoms of left ventricular failure and diseases that night influence pulmonary pressures, and if drugs affecting cardiac performance could be withdrawn safely for 3 days. Ten healthy subjects served as control group. The mean pulmonary capillary wedge pressure and mean pulmonary artery pressure were similar in both groups. In contrast, the systolic pulmonary arterial pressure exceeded 30 mm Hg in 6 patients. Mean pulmonary vascular resistance was higher in examined patients than in the control group. Right ventricular end-diastolic pressure was above 5 mm Hg in as much as 50% of patients. Mean systolic ejection rate showed a tendency to decrease. The results indicate that part of patients with primary arterial hypertension exhibits disorders in the pulmonary circulation and right ventricular performance.     

Sildenafil is more selective pulmonary vasodilator than prostaglandin E1 in patients with pulmonary hypertension due to heart failure

In some patients, heart failure (HF) is associated with increased pulmonary vascular resistance (PVR). The magnitude and the reversibility of PVR elevation affect the HF management. Sildenafil has been recently recognized as potent PVR-lowering drug in HF. The aim of the study was to compare hemodynamic effects and pulmonary selectivity of sildenafil to prostaglandin E(1) (PGE(1)). Right-heart catheterization was performed in 13 euvolemic advanced HF patients with elevated PVR (6.3+/-2 Wood's units). Hemodynamic parameters were measured at the baseline, during i.v. infusion of PGE1 (alprostadil 200 ng · kg(-1) · min(-1)) and after 40 mg oral dose of sildenafil. Both drugs similarly reduced systemic vascular resistance (SVR), but sildenafil had higher effect on PVR (-28 % vs. -49 %, p = 0.05) and transpulmonary pressure gradient than PGE(1). The PVR/SVR ratio--an index of pulmonary selectivity, did not change after PGE(1) (p = 0.7) but it decreased by -32 % (p = 0.004) after sildenafil. Both drugs similarly reduced pulmonary artery mean and wedge pressures and increased cardiac index (+27 % and +28 %). Sildenafil led more often to transplant-acceptable PVR while causing smaller drop of mean systemic pressure than PGE(1). In conclusion, vasodilatatory effects of sildenafil in patients with heart failure are more pronounced in pulmonary than in systemic circulation.     

Effects of pericardial constraint and ventricular interaction on left ventricular hemodynamics in the unloaded heart

Pericardial constraint and ventricular interaction influence left ventricular (LV) performance when preload is high. However, it is unclear if these constraining forces modulate LV filling when the heart is unloaded, such as during upright posture, in humans. Fifty healthy individuals underwent right heart catheterization to measure pulmonary capillary wedge (PCWP) and right atrial pressure (RAP). To evaluate the effects of pericardial constraint on hemodynamics, transmural filling pressure (LVTMP) was defined as PCWP-RAP. Beat-to-beat blood pressure (BP) waveforms were recorded, and stroke volume (SV) was derived from the Modelflow method. After measurements at -30 mmHg lower body negative pressure (LBNP), which approximates the upright position, LBNP was released, and beat-to-beat measurements were performed for 15 heartbeats. At -30 mmHg LBNP, RAP and PCWP were significantly decreased. During the first six beats of LBNP release, heart rate (HR) was unchanged, while BP increased from the fourth beat. RAP increased faster than PCWP resulting in an acute decrease in LVTMP from the fourth beat. A corresponding drop in SV by 3% was observed with no change in pulse pressure. From the 7th to 15th beats, LVTMP and SV increased steadily, followed by a decreased HR due to the baroreflex. A decreased TMP, but not PCWP, caused a transient drop in SV with no changes in HR or pulse pressure during LBNP release. These results suggest that the pericardium constrains LV filling during LBNP release, enough to cause a small but significant drop of SV, even at low cardiac filling pressure in healthy humans.     

Rapid ventricular pacing of dogs to heart failure: biochemical and physiological studies

Chronic, rapid ventricular pacing produces congestive heart failure in dogs. The objectives of this study were to determine whether or not (i) in vitro myocardial biochemical alterations reported for heart failure by volume or pressure overload also occurred with heart failure due to rate overload, and (ii) these biochemical alterations were related to relevant in vivo cardiac physiologic alterations. We compared 27 dogs that were paced to advanced heart failure with 21 sham-operated dogs. Dogs with heart failure had 55% lower left ventricular ejection fraction (22.5 +/- 7.6 vs. 50.5 +/- 5.1%) and cardiac index (81 +/- 22 vs. 178 +/- 48 mL.min-1.kg-1), 287% higher pulmonary capillary wedge pressure (27.5 +/- 6.8 vs. 7.1 +/- 3.4 mmHg; 1 mmHg = 133.3 Pa), and 64% greater left ventricular diastolic area (18.4 +/- 3.7 vs. 11.2 +/- 1.3 cm2) (all p less than 0.05). Dogs with heart failure also had (i) 69% lower norepinephrine (232 +/- 139 vs. 747 +/- 220 ng/g protein), (ii) 25-50% lower activities of myofibrillar Ca ATPase (0.188 +/- 0.026 vs. 0.253 +/- 0.051 U/mg myofibrils), sarcoplasmic reticulum Ca-transport ATPase (0.155 +/- 0.074 vs. 0.288 +/- 0.043 U/mg membrane), and the glycolytic enzyme phosphofructokinase (33.4 +/- 10.0 and 47.7 +/- 15.8 U/g), (iii) 32% higher activity of the beta-oxidation enzyme hydroxyacyl-CoA dehydrogenase (11.43 +/- 1.48 vs. 8.67 +/- 1.70 U/g), and (iv) 60% higher activity of Krebs cycle oxoglutarate dehydrogenase (2.89 +/- 0.77 vs. 1.81 +/- 0.95 U/g) (all p less than 0.05). No differences between groups were observed for isozyme patterns and ATPase activity of myosin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Additive antianginal effect of verapamil in patients receiving propranolol

Ten men with stable angina pectoris not fully relieved by optimal doses of propranolol (mean 218 mg daily) were given a single oral dose of 120 mg verapamil or a placebo on alternate mornings; the order of treatment was double blind. Patients had trained in a protocol that precipitated angina after three to six minutes of exercise on a bicycle ergometer. On test days, and with continued propranolol treatment, bicycle exercise was performed just before the administration of verapamil or placebo and hourly thereafter for eight hours. Mean exercise tolerance was 118 seconds greater one hour after verapamil than one hour after placebo (p <0·001), and a significant though somewhat diminished difference of 66 seconds was still present at six hours (p <0·01). Verapamil lowered resting systolic blood pressure by 12 mm Hg (p <0·01) without changing heart rate. None of the 10 patients showed adverse effects from the verapamil-propranolol combination.The results of this study suggest that verapamil is a highly effective antianginal supplement to propranolol.     

Obesity Is Associated with Lower Coronary Microvascular Density

Background

Obesity is associated with diastolic dysfunction, lower maximal myocardial blood flow, impaired myocardial metabolism and increased risk of heart failure. We examined the association between obesity, left ventricular filling pressure and myocardial structure.

Methods

We performed histological analysis of non-ischemic myocardium from 57 patients (46 men and 11 women) undergoing coronary artery bypass graft surgery who did not have previous cardiac surgery, myocardial infarction, heart failure, atrial fibrillation or loop diuretic therapy.

Results

Non-obese (body mass index, BMI, ≤30 kg/m², n=33) and obese patients (BMI >30 kg/m², n=24) did not differ with respect to myocardial total, interstitial or perivascular fibrosis, arteriolar dimensions, or cardiomyocyte width. Obese patients had lower capillary length density (1145±239, mean±SD, vs. 1371±333 mm/mm³, P=0.007) and higher diffusion radius (16.9±1.5 vs. 15.6±2.0 μm, P=0.012), in comparison with non-obese patients. However, the diffusion radius/cardiomyocyte width ratio of obese patients (0.73±0.11 μm/μm) was not significantly different from that of non-obese patients (0.71±0.11 μm/μm), suggesting that differences in cardiomyocyte width explained in part the differences in capillary length density and diffusion radius between non-obese and obese patients. Increased BMI was associated with increased pulmonary capillary wedge pressure (PCWP, P<0.0001), and lower capillary length density was associated with both increased BMI (P=0.043) and increased PCWP (P=0.016).

Conclusions

Obesity and its accompanying increase in left ventricular filling pressure were associated with lower coronary microvascular density, which may contribute to the lower maximal myocardial blood flow, impaired myocardial metabolism, diastolic dysfunction and higher risk of heart failure in obese individuals.