Search

Pulmonary hypertension (PH) in left heart disease, classified as group II, is the most common form of PH that occurs in approximately 60% of cases of reduced and preserved left ventricular ejection fraction. Although relatively much is known about hemodynamic stages (passive or reactive) and their consequences on the right ventricle (RV) there is no consensus on the best hemodynamic definition of group II PH. In addition, the main pathways that lead to lung capillary injury and impaired biology of small artery remodelling processes are largely unknown. Typical lung manifestations of an increased pulmonary pressure and progressive RV-pulmonary circulation uncoupling are an abnormal alveolar capillary gas diffusion, impaired lung mechanics (restriction), and exercise ventilation inefficiency. Of several classes of pulmonary vasodilators currently clinically available, oral phosphodiesterase 5 inhibition, because of its strong selectivity for targeting the cyclic guanosine monophosphate pathway in the pulmonary circulation, is increasingly emerging as an attractive opportunity to reach hemodynamic benefits, reverse capillary injury, and RV remodelling, and improve functional capacity. Guanylate cyclase stimulators offer an additional intriguing opportunity but the lack of selectivity and systemic effects might preclude some of the anticipated benefits on the pulmonary circulation. Future trials will determine whether new routes of pharmacologic strategy aimed at targeting lung structural and vascular remodelling might affect morbidity and mortality in left heart disease populations. We believe that this therapeutic goal rather than a pure hemodynamic effect might ultimately emerge as an important challenge for the clinician., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Epidemiological information on patients with acute coronary syndromes managed in specialized cardiac centres is limited., Objective: To report the evolution of demographics, treatment and outcome of patients admitted to a tertiary coronary care unit (CCU) over a 17-year period., Methods: A prospective database of 18,719 patients admitted from April 1986 to March 2003 in a 21-bed CCU was analyzed., Results: From 1986 to 2003, the number of admissions increased from 937 to 1577 per year, while the length of stay declined from 7.5 to 3.5 days. The mean age increased from 58.4 to 63.4 years, and the proportion of men remained stable at approximately 70%. The use of coronary angiograms increased from 49.8% to 81.1% in all patients, while fibrinolysis dropped to 0.4%. In-hospital mortality decreased from 9% to 1.5%. The percentage of overall instrumentation (arterial line, central venous catheter, temporary pacemaker, Swan-Ganz catheter and intra-aortic balloon pump) decreased from 38% to 8.1%. From 1995 to 2003, the proportion of stenting during percutaneous transluminal coronary angioplasty increased dramatically from 0% to 86%. In the past five years, surgical revascularization has remained stable at approximately 20% of all admissions. The proportion of patients discharged with a noncoronary chest pain diagnosis has remained constant at approximately 4%., Interpretation: There has been a tremendous increase in efficiency, with an approximate doubling of the admissions turnover rate in a tertiary CCU. Patients with acute coronary syndromes are stratified faster and treated more invasively. Therapeutic advances are reflected by an almost linear 0.5% per year decrease in in-hospital mortality.

Endothelial dysfunction is an early event in the continuum of the pathogenesis of atherosclerosis that persists throughout the disease process. Endothelial dysfunction may be a valuable marker or barometer of the composite effect of the various predisposing factors, even some yet unknown, on the subsequent risk of cardiovascular events. Accumulating data suggest that clinical evaluation of endothelial function may provide incremental value to current risk stratification and to the tailoring of pharmacological and nonpharmacological therapy. This has prompted many investigators to probe the integrity of endothelium-dependent vascular reactivity in an effort to uncover clinically useful methods of evaluating endothelial function. For practical purposes, reactive hyperemia of the forearm has become the most popular stimulus for testing vascular reactivity, and several methods have been developed to quantify this response and study its determinants. High-resolution brachial ultrasound and venous impedance plethysmography are used extensively in mechanistic studies; however, for practical purposes, it is unlikely that these methods could be used in routine clinical practice. Therefore, some alternatives are being actively developed. The greatest remaining challenge is to find firm evidence that endothelial function can be used as a clinical surrogate of cardiovascular events. Validation of these methods and their evaluation in large-scale trials is needed to determine whether abnormal vascular reactivity is indeed a good barometer of cardiovascular risk.

Endothelin (ET) -1 is a potent vasoconstrictor and promitogenic peptide produced by the vascular endothelium. The ET system is activated in atherosclerosis and in most cardiovascular conditions associated with increased vascular tone and remodelling. There are two ET-receptor (ET-R) subtypes: the ETA-Rs mediate smooth muscle vasoconstriction and proliferation, and the more complex ETB-Rs have antagonistic actions - they serve a dual role of clearance and vasodilation in the endothelium, while in smooth muscle cells they also provoke vasoconstriction. Selective ETA-R and nonselective ETA/B-R antagonists are entering the clinical development phase. These agents have shown their effectiveness in the therapy of various models of heart failure, pulmonary hypertension, systemic hypertension and ischemia-reperfusion and in the prevention of restenosis. In patients with congestive heart failure, short term ET-antagonist (ET-R) therapy provides hemodynamic and symptomatic improvement. Because of the dual role of the ETB-R, nonselective antagonists may provide greater or fewer benefits than selective ETA-R antagonists: a lack of direct comparison of the two categories of agents, however, does not allow this distinction at present. In the evaluation of this new class of therapeutic agents, particular attention should be paid to potency and receptor selectivity of a compound, the alterations in ETA-R and ETB-R activity brought on by pathological conditions, the proportions of ETA versus ETB-R of the target system, and finally, the net importance of the possible protective role of the endothelial ETB versus the deleterious effects of the smooth muscle ETB-R.

Objective: To assess the efficacy and side effects of routine premedication in patients undergoing cardiac catheterization procedures in a tertiary cardiac care institute. The criteria used included: arterial hemoglobin oxygen saturation (%SaO2), level of sedation and level of anxiety before and after the procedure. Overall patient satisfaction was also quantified., Design: Sixty-two adult patients scheduled for cardiac catheterization procedures were recruited for the study. They were premedicated with one of several premedication regimens: oral diazepam 5 to 10 mg; oral lorazepam 1 mg; oral diazepam 10 mg+oral promethazine 25 mg; or oral diazepam 10 mg+oral diphenhydramine 25 mg. No attempt was made to control the premedication the patients received; it was ordered by each patient's cardiologist according to personal preference. Patients underwent pulse oximetry and evaluation of sedation, anxiety and level of satisfaction before and after cardiac catheterization., Results: All patients tested had values for mean precatheterization %SaO2 above 92%. No patient had postcatheterization %SaO2 readings below that defined as indicating clinically significant hypoxemia (%SaO2 less than 90%). Patients were awake or lightly sedated before and after cardiac catheterization. Thirteen per cent of patients suffered from high levels of anxiety before, and 16% during, cardiac catheterization. Twenty-three per cent of patients reported being dissatisfied with the premedication before, and 10% of patients reported being dissatisfied during, cardiac catheterization., Conclusions: Clinically significant hypoxemia and oversedation are not problems for most patients given the types and doses of precatheterization medication used in the study population. The premedication schedules followed in the study failed to provide satisfaction and anxiolysis in a significant number of those studied.

Tolerance to the continuous intravenous infusion of nitroglycerin is thought to be largely the result of a decrease in vascular responsiveness, possibly due to intra-smooth muscle sulfhydryl group depletion. Another mechanism proposed to contribute to tolerance is nitroglycerin-induced reflex neurohumoral activation resulting in vasoconstriction and sodium and water retention. It has been proposed that the sulfhydryl group-containing angiotensin converting enzyme (ACE) inhibitor captopril may be useful in preventing tolerance to nitroglycerin by repleting sulfhydryl groups and by decreasing reflex neurohumoral activation. However, by decreasing renal perfusion pressure, the combination of captopril and nitrates could also lead to renal dysfunction. The objectives of this study were to determine whether captopril prevented or significantly reduced hemodynamic tolerance to a 72 h infusion of nitroglycerin, and to determine whether the combination of nitroglycerin and captopril caused deterioration of renal function. Nineteen patients with congestive heart failure received nitroglycerin (1.5 micrograms/kg/min) alone (n = 11) or in combination with oral captopril (63 +/- 8 mg/day) (n = 8). In both groups, partial hemodynamic tolerance developed within the first 24 h of nitroglycerin infusion. Nitroglycerin therapy, with or without captopril, did not affect plasma adrenaline, noradrenaline, aldosterone or arginine vasopressin. However, plasma renin activity increased and atrial natriuretic peptide decreased in both groups, these changes being significant after 1 h of infusion but gradually returning towards baseline, in both groups, over the next 71 h. The nitroglycerin infusion did not alter body weight, urine output, creatinine clearance or fractional sodium excretion in either group.(ABSTRACT TRUNCATED AT 250 WORDS)