A comparison of the assessment and management of cardiometabolic risk in patients with and without type 2 diabetes mellitus in Canadian primary care.

AIM: To investigate the cardiometabolic risk (CMR) assessment and management patterns for individuals with and without type 2 diabetes mellitus (T2DM) in Canadian primary care practices. METHODS: Between April 2011 and March 2012, physicians from 9 primary care teams and 88 traditional non-team practices completed a practice assessment on the management of 2461 patients >40 years old with no clinical evidence of cardiovascular disease and diagnosed with at least one of the following risk factor-T2DM, dyslipidaemia or hypertension. RESULTS: There were 1304 individuals with T2DM and 1157 without. Pharmacotherapy to manage hyperglycaemia, dyslipidaemia and hypertension was widely prescribed. Fifty-eight percent of individuals with T2DM had a glycated haemoglobin (HbA1c) ≤7.0%. Amongst individuals with dyslipidaemia, median low-density lipoprotein cholesterol (LDL-C) was 1.8 mmol/l for those with T2DM and 2.8 mmol/l for those without. Amongst individuals with hypertension, 30% of those with T2DM achieved the <130/80 mmHg target, whereas 60% of those without met the <140/90 mmHg target. The composite glycaemic, LDL-C and blood pressure (BP) target outcome was achieved by 12% of individuals with T2DM. Only 17% of individuals with T2DM and 11% without were advised to increase their physical activity. Dietary modifications were recommended to 32 and 10% of those with and without T2DM, respectively. CONCLUSIONS: Patients at elevated CMR were suboptimally managed in the primary care practices surveyed. There was low attainment of recommended therapeutic glycaemic, lipid and BP targets. Advice on healthy lifestyle changes was infrequently dispensed, representing a missed opportunity to educate patients on the long-term benefits of lifestyle modification.

Poor achievement of guidelines-recommended targets in type 2 diabetes: findings from a contemporary prospective cohort study.

AIMS: To prospectively evaluate diabetes management in the primary care setting and explore factors related to guideline-recommended triple target achievement [blood pressure (BP) ≤ 130/80 mmHg, A1C ≤ 7% and low-density lipoprotein (LDL)-cholesterol < 2.5 mmol/l]. METHODS: Baseline, 6 and 12 month data on clinical and laboratory parameters were measured in 3002 patients with type 2 diabetes enrolled as part of a prospective quality enhancement research initiative in Canada. A generalised estimating equation model was fitted to assess variables associated with triple target achievement. RESULTS: At baseline, 54%, 53% and 64% of patients, respectively, had BP, A1C and LDL-cholesterol at target; all three goals were met by 19% of patients. The percentage of individuals achieving these targets significantly increased during the study [60%, 57%, 76% and 26%, respectively, at the final visit, p < 0.0001 except for A1C, p = 0.27]. A much smaller proportion of patients had adequate control during the entire study period [30%, 39%, 53% and 7%, respectively]. In multivariable analysis, women, patients younger than 65 years and patients of Afro-Canadian origin were less likely to achieve the triple target. DISCUSSION: As part of a quality enhancement research initiative, we observed important improvements in the attainment of guidelines-recommended targets in patients with type 2 diabetes followed for a 12-month period in the primary care setting; however, many individuals still failed to achieve and especially maintain optimal goals for therapy, particularly the triple target. Results of the multivariable analysis reinforce the need to address barriers to improve diabetes care, particularly in more susceptible groups.

Efficacy and side-effects of cyclosporine dose monitoring with levels 6 h after the morning dose in heart transplant patients.

The purpose of this study was to compare CsA dose monitoring with trough levels (T0) vs. levels obtained 6 h after the morning dose of CsA (T6), with respect to the incidence of acute rejection and renal dysfunction, and the cumulative dose, as well as the cost of CsA after heart transplantation. Twenty consecutive adult heart transplant patients receiving quadruple sequential immunosuppression were prospectively randomized into CsA monitoring with T0 (Group I) vs. T6 levels (Group II). Oral CsA was started at a dosage of 2 mg/kg/d, 1-4 d after transplantation. The target range for either T0 or T6 was 150 to 250 ng/ml (enzyme multiplied immunologic technique), respectively. The CsA dose was increased or decreased by 0.5-1 mg/kg/d if the measured level was outside of the target range. Throughout the follow-up period (Group I, 11 +/- 2 months; Group II, 10 +/- 3 months), the incidence of acute rejection (ISHLT grade > or = 2) was 50% in each group. The left ventricular ejection fraction and serum creatinine were similar in both groups at 1 month and at the end of the follow-up. The maximal dose of CsA (mg/kg/d): 3.8 +/- 1 vs. 5 +/- 0.6 (P = 0.002), the minimal dose: 2.2 +/- 0.7 vs. 3.4 +/- 0.8 (P = 0.003), and the current dose: 2.6 +/- 0.6 vs. 3.5 +/- 1 (P = 0.02), were lower in Group II, as well as the cumulative dose of CsA (mg): 61,790 +/- 19,754 vs. 88,524 +/- 18,082 (P = 0.005), and its cost (CDN$): 3,589 +/- 1,116 vs. 5,106 +/- 1,045 (P = 0.005). In conclusion, CsA dose monitoring with T6 was associated with a 30% lower CsA dose and cost compared to T0, with the same effectiveness in the prevention of acute rejection, and similar cardiac and renal function.

Time varying loading of the pulmonary circulation: a model to describe hemodynamic observations in the stiff left atrial syndrome.

OBJECTIVE: To develop a mathematical model that could explain the following observations: that right heart failure can develop in association with no other cardiac abnormality than a severe reduction in the compliance of the left atrium; and that patients with this syndrome have systolic pulmonary hypertension with left atrial v waves in the absence of either mitral regurgitation or left ventricular dysfunction. DESIGN: A model of the pulmonary circulation was designed with a time varying terminal hydraulic load, which was varied between a noncompliant left atrium during systole and a compliant left ventricle/left atrium combination during diastole. Using representative parameters and a pulmonary arterial flow wave as input, pressures in the pulmonary artery and left atrium and right ventricular power output were calculated. RESULTS: Pulmonary arterial and left atrial systolic pressures are increased as left atrial compliance is reduced. The time varying change in terminal load results in an increase in systolic pressures, whereas diastolic pressures remain normal. A decrease in left atrial compliance increases both the nonpulsatile and pulsatile components of pulmonary input impedance, whereas only the nonpulsatile component of right ventricular power output is increased. CONCLUSIONS: The time varying pulmonary load model of the pulmonary circulation, in the presence of a reduced left atrial compliance results in pulmonary, and left atrial pressures similar to those observed in patients with the stiff left atrial syndrome. The resulting increase in right ventricular power output could be an important factor in the development of right heart failure.

Aortofemoral transfer function: a method to determine the instantaneous aortic valve gradient in aortic valve stenosis.

OBJECTIVES: This study was performed to evaluate the use of synthesized ascending aorta pressure, calculated from femoral artery pressure using an aortofemoral transfer function, in the assessment of aortic valve stenosis. BACKGROUND: Measurement of an accurate aortic valve gradient in patients with aortic stenosis often requires simultaneous recordings of ascending aorta and left ventricular pressures. The use of femoral artery pressure is considered to be a poor substitute for ascending aorta pressure. However, the aortic pressure wave can be calculated from the femoral artery pressure if the aortofemoral transfer function has been determined. METHOD: Femoral artery pressure from the side arm of an introducer sheath and ascending aorta pressure are recorded simultaneously and the data stored in a personal computer. An aortofemoral transfer function is determined from the ratio of the Fourier components of aortic and femoral pressures. Left ventricular and femoral artery pressures are then recorded. Using the previously determined transfer function, the simultaneous ascending aorta pressure is calculated from the femoral pressure. RESULTS: Ascending aorta pressure waveforms estimated from femoral artery pressure closely resembled the simultaneously recorded ascending aorta pressure. Mean aortic valve gradients calculated from the synthesized aortic pressure correlated well with the gradient measured from direct recordings of aortic pressure (r = 0.98). There was also a good relation between valve areas (r = 0.93) and valve resistances (r = 0.98) calculated using the two methods. CONCLUSIONS: Using current computer technology, accurate aortic valve gradients can be rapidly calculated using femoral artery pressure as a substitute for ascending aorta pressure. This technique will reduce the need and risks of multiple catheters to determine aortic valve gradients.

A method of dynamic analysis of iodine-123-metaiodobenzylguanidine scintigrams in cardiac mechanical overload hypertrophy and failure.

Cardiac sympathetic neuronal degeneration accompanies mechanical overload heart failure. We hypothesized that sympathetic nerve and myocyte failure share a common etiology and that 123I-metaiodobenzylguanidine (MIBG) might provide a precise method of detecting failure in chronic mechanical overload. Our aim was to develop a method for the dynamic analysis of 123I-MIBG scintigrams which could yield a quantitative index of myocardial sympathetic neuronal function in this condition. We performed serial 123I-MIBG scintigraphy in 33 volunteers, 10 orthotopic cardiac transplant recipients and 26 patients with chronic mechanical overload of the left ventricle. We constructed a compartmental model in which total heart activity represents the sum of cardiac sympathetic vesicular and cytosolic pools. Patients with antecedent mechanical overload heart failure or myocardial dysfunction had accelerated myocardial egress of tracer that we ascribed to a specific impairment in vesicular storage rather than to a more rapid turnover of an intact vesicular pool.

LV-arterial coupling: interactive model to predict effect of wave reflections on LV energetics.

The interaction between the left ventricle (LV) and the arterial system was simulated using sequential convolution of the flow output generated by a time-varying elastance model of the LV with an impulse response calculated from a 128-element model of the arterial system. The model illustrates the effect of independent changes of components of the arterial load on LV performance and energetics. This report studies the response of the model LV to an increase in arterial resistance, a decrease in arterial compliance, and an increase in discrete vascular reflections. Although arterial resistance exerts the greatest effect on ventricular stroke output, a reduction of arterial compliance or an increase in early reflections resulted in less optimal coupling of the heart to the arteries and less efficient energy utilization by the LV. In addition, the earlier the reflections return, the greater the disturbance of ventricular arterial coupling.

Assigning priority to patients requiring coronary revascularization: consensus principles from a panel of cardiologists and cardiac surgeons.

In light of lengthy waiting lists for coronary surgery in Canada, a panel of 16 cardiologists and cardiac surgeons was convened to derive guiding principles for ranking how urgently diverse patients with angiographically proven coronary disease require revascularization. Factors likely to affect urgency were agreed upon by the panelists and incorporated into a case scenario questionnaire. Each panelist then rated 438 case scenarios with respect to maximum acceptable waiting time on a scale with seven time frames ranging from emergency surgery ('level 1') to delays of up to six months ('level 7'). The scenario rating process facilitated attainment of a panel consensus. The purpose of the principles is to assist in assigning priorities to patients according to both symptoms and risk of death or additional morbidity from ischemic events. The pattern or severity of the patient's anginal symptoms and the response of those symptoms to medical therapy emerged as the single most important determinant of the level of urgency. Anatomy and noninvasive tests of ischemic risk were the other key determinants of priority. All other factors were less important, and operated largely within a given level of urgency on the seven-point scale. The principles, including explicit ranking criteria divided according to angina class, are outlined in this final report. The panel specifically cautioned that adoption of such principles is not designed to countenance delays in treatment, but if necessary, should help form more rational queues for coronary revascularization.

A Canadian multicentre study of a 48 h infusion of milrinone in patients with severe heart failure.

Milrinone is a nonglycoside, nonsympathomimetic bipyridine with positive inotropic and systemic vasodilator properties. In order to evaluate the efficacy and safety of a short term infusion of milrinone, 105 patients with stable New York Heart Association (NYHA) class III or IV heart failure received a loading dose (50 micrograms/kg) and a 48 h continuous infusion (0.5 micrograms/kg/min). Administration of the loading dose resulted in a 28% decrease in pulmonary capillary wedge pressure (PCWP) (P less than 0.001), a 38% increase in cardiac index (P less than 0.001), and a 34% increase in stroke volume index (P less than 0.001) within 15 mins. Milrinone infusion maintained an average 27% and 24% reduction in PCWP during the first and second days, respectively (P less than 0.001). Cardiac index was 32% and 34% above baseline during the same intervals (P less than 0.001). There were no clinically significant changes in heart rate or mean arterial blood pressure during the study period. In a subset of 47 patients who underwent Holter monitoring before and during infusion, a significant increase in ventricular arrhythmias (premature ventricular complexes per hour, ventricular couplets per hour and ventricular runs greater than or equal to three) was demonstrated (P less than 0.0001). In general, milrinone was well tolerated. Of the 105 patients entered, one died of an acute myocardial infarction after premature termination of the infusion, and the infusion rate was decreased in two others because of supraventricular arrhythmias. In patients with severe heart failure, intravenous milrinone has significant beneficial hemodynamic effects. ECG monitoring for arrhythmias is recommended during milrinone infusion.

Inspiratory reduction in left heart filling as a mechanism of pulsus paradoxus in cardiac tamponade.

Pulsus paradoxus occurs in cardiac tamponade because the output of the left ventricle falls during inspiration. The principal cause for this is reduced filling of the left ventricle during the preceding diastole. The present study examines whether this reduced filling of the left ventricle on inspiration is due to compression by the right heart or due to reduced venous return to the left heart. The effect of pericardial tamponade on hemodynamics and left ventricular and atrial volumes was determined in six experimental animals. The data demonstrate that from the outset pericardial fluid reduces left ventricular end diastolic volume, although initially left ventricular end systolic volume decreases as well. By contrast, pulsus paradoxus is a relatively late phenomenon occurring with severe tamponade and associated with an inspiratory decrease in left atrial and ventricular volumes in the face of a drop in left ventricular filling pressure. Underfilling of the left heart is the most likely cause of this combination of events.

Radial arterial pressure measurements may be a poor guide to the beneficial effects of nitroprusside on left ventricular systolic pressure in congestive heart failure.

The effect of nitroprusside on pressure wave transmission from ascending aorta to radial artery was studied in 10 patients with severe congestive heart failure. Nitroprusside resulted in a beneficial increase in cardiac index, reduction of pulmonary wedge pressure and reductions of aortic and radial arterial mean pressures. In 6 patients with an identifiable late systolic peak of aortic pressure (group I), nitroprusside reduced aortic systolic pressure more than radial systolic pressure, resulting in an increase in the difference between aortic and radial systolic arterial pressure (group I control 13 +/- 4, nitroprusside 20 +/- 6 mm Hg; p less than 0.025). Yet in 4 patients in whom no aortic late systolic pressure wave was apparent (group II), nitroprusside did not alter the difference between aortic and radial systolic pressures. Radial arterial pressure is often used to estimate the effect of nitroprusside on the arterial pressure load on the left ventricle. These results indicate that a reduction of radial systolic pressure induced by nitroprusside may underestimate the true reduction of aortic systolic pressure and thus the effect of the vasodilator on the arterial load on the left ventricle. The enhanced difference between aortic and radial arterial systolic pressures appears to be the consequence of nitroprusside on arterial pressure reflections.

Dyslipoproteinemias after heart and heart-lung transplantation: potential relation to accelerated graft arteriosclerosis.

Plasma lipid, lipoprotein lipid, and low-density lipoprotein (LDL) apolipoprotein B (Apo B) levels were measured in 34 patients who had undergone heart transplantation and in two patients who had undergone heart-lung transplantation. In contrast to initial reports, atherogenic dyslipoproteinemias were common, with 14% of patients having increased LDL cholesterol levels, 16.7% increased triglyceride levels, 8.3% decreased high-density lipoprotein (HDL) cholesterol levels, and 22.2% increased LDL Apo B levels. Of interest, 14% of patients had an HDL cholesterol level greater than the 95th percentile of the general population. In four patients coronary arteriosclerosis developed after transplantation. All had an atherogenic dyslipoproteinemia. One had type II hypercholesterolemia, and one had isolated low HDL cholesterol levels. Two had hyperapobetalipoproteinemia, one of whom also had low HDL cholesterol levels. The results establish that atherogenic dyslipoproteinemias are frequent in patients after heart transplantation and suggest that these dyslipoproteinemias, along with rejection, may play a role in the pathogenesis of arteriosclerosis after transplantation.

Reflected pressure waves in the ascending aorta: effect of glyceryl trinitrate.

Reflected pressure waves returning to the ascending aorta are an important contribution to aortic systolic pressure and thus the load on the left ventricle. The effect of glyceryl trinitrate on pressure wave reflections in the ascending aorta was studied using the transmission of arterial pressure between two high fidelity pressure transducers. Glyceryl trinitrate 0.3 mg sublingually reduced systolic arterial pressure by 11 mmHg owing to a reduction of the late systolic pressure peak. Mean arterial pressure fell 2 mmHg, but heart rate and aortic flow did not change. The aortic input impedance was reduced at the first harmonic (control 18.4(4.1); glyceryl trinitrate 10.8(2.4) kPa.s.litre-1; p less than 0.005) but characteristic impedance was not changed (control 12.7(3.8); glyceryl trinitrate 14.2(3.3) kPa.s.litre-1). The first two harmonics of apparent phase velocity were reduced by glyceryl trinitrate (1.05 Hz: control 3314(798); glyceryl trinitrate 1772(495) cm.s-1; p less than 0.01; 2.1 Hz: control 1246(269); glyceryl trinitrate 754(127) cm.s-1; p less than 0.05), yet the foot to foot wave velocity was unchanged (control 688(112); glyceryl trinitrate 726(112) cm.s-1). There was a significant reduction in the amplitude of the global reflection coefficient at 1.05 Hz (control 0.70(0.09); glyceryl trinitrate 0.48(0.08); p less than 0.001) and at 2.1 Hz (control 0.48(0.07); glyceryl trinitrate 0.23(0.06); p less than 0.005) with no significant change in phase. Glyceryl trinitrate reduces cardiac pulsatile load by diminishing the amplitude of wave reflections arriving back in the aorta during systole yet has no effect on aortic compliance or arteriolar resistance. This study demonstrates a method of evaluating the effect of vasoactive drugs on cardiac pulsatile load.

Effect of nitroglycerin on left ventricular hydraulic load.

It has previously been shown that nitroglycerin increases the compliance of forearm arteries. The present study investigates whether nitroglycerin reduces the hydraulic load on the heart (as measured by aortic input impedance) by a mechanism compatible with an increase in peripheral arterial compliance. In eight subjects, measurements of aortic flow and pressure were made with a catheter tipped probe before and during intravenous nitroglycerin (6 to 30 micrograms/min) administration. The reduction of aortic systolic pressure (129 +/- 5 to 113 +/- 4 mmHg, P less than 0.001) was due to a decrease in the late systolic pressure peak. There was no change in stroke volume, heart rate or systemic vascular resistance. The lower systolic pressure resulted from a decrease in the amplitude of the first harmonic of input impedance (210 +/- 19 to 143 +/- 11 dyne.s.cm-5, P less than 0.005) yet characteristic impedance (a measure of local aortic distensibility) did not change. The ratio of maxima to minima of the impedance spectrum was reduced (1.02 +/- 0.09 to 0.71 +/- 0.11, P less than 0.05) suggesting a decrease in the amplitude of reflected waves contributing to aortic impedance. Nitroglycerin at doses which have no effect on arteriolar resistance vessels, reduces systolic aortic pressure by diminishing the amplitude of wave reflections returning to the ascending aorta in late systole. This mechanism is compatible with the peripheral arterial effects of nitroglycerin.

Forearm arterial compliance: a new measure of arterial compliance?

This study has investigated the origin of the pulsatile expansion of the forearm recorded by the amplification of the pulsatile signal derived from a mercury in rubber plethysmograph. Venous occlusion to pressures of 40 mmHg had no effect on the amplitude of the volume pulse, suggesting that the volume pulse originates in vessels distended by pressures above this level. Nitroglycerin in small doses (0.15 mg sublingual) increased the amplitude of the volume pulse without changing forearm vascular resistance, consistent with an arterial origin of the forearm volume pulse. The instantaneous relationship between the volume pulse and arterial pressure (forearm compliance) showed that nitroglycerin increased the volume pulse in association with a reduction in pulse pressure. As the volume pulse probably originates in the arterial system, the increase in forearm compliance is a measure of the increase in arterial compliance induced by nitroglycerin. Both the volume pulse and forearm compliance may be useful indicators of the effect of physiological and pharmacological interventions on the distensile properties of arteries.

Right ventricular dilated cardiomyopathy.

Fourteen patients with predominantly right sided dilated cardiomyopathy were studied, of whom five died suddenly. The condition is characterised by male preponderance, syncope, ventricular tachycardia, which typically has a left bundle branch block pattern on the surface electrocardiogram, and right heart failure. The diagnosis should be considered in patients presenting with otherwise unexplained ventricular tachycardia or syncope; the diagnosis may be readily missed because of the nonspecific nature or absence of signs.