Faculty Bibliography

BACKGROUND: Hypertension is the major risk factor for cardiovascular (CV) disease such as myocardial infarction (MI) and stroke. This risk is well known to extend into the perioperative period. Although most perioperative hypertension can be managed with the patient's outpatient regimen, there are situations in which oral medications cannot be administered and parenteral medications become necessary. They include postoperative nil per os status, severe pancreatitis, and mechanical ventilation. This article reviews the management of perioperative hypertensive urgency with parenteral medications. METHODS: A PubMed search was conducted by cross-referencing the terms 'perioperative hypertension,' 'hypertensive urgency,' 'hypertensive emergency,' 'parenteral anti-hypertensive,' and 'medication.' The search was limited to English-language articles published between 1970 and 2008. Subsequent PubMed searches were performed to clarify data from the initial search. RESULTS: As patients with hypertensive urgency are not at great risk for target-organ damage (TOD), continuous infusions that require intensive care unit (ICU) monitoring and intraarterial catheters seem to be unnecessary and a possible misuse of resources. CONCLUSIONS: When oral therapy cannot be administered, patients with hypertensive urgency can have their blood pressure (BP) reduced with hydralazine, enalaprilat, metoprolol, or labetalol. Due to the scarcity of comparative trials looking at clinically significant outcomes, the medication should be chosen based on comorbidity, efficacy, toxicity, and cost

Dosing equivalency of carvedilol and metoprolol remains a debate. Degree of beta 1-blockade is best assessed by blunting of the exercise-induced heart rate. Accordingly, the authors have investigated dosing equivalency by examining baseline and peak exercise heart rates and norepinephrine levels in subjects with chronic heart failure treated with carvedilol or metoprolol. Thirty-seven subjects treated with carvedilol (32.9 +/- 3.5 mg; n = 23) or metoprolol succinate (XL) (96.4 +/- 15.9 mg; n = 14) referred for cardiopulmonary exercise testing were studied prospectively. Carvedilol versus metoprolol XL subjects did not differ with respect to baseline heart rate (73 +/- 2 vs 70 +/- 3 bpm), or baseline plasma norepinephrine levels (597.5 +/- 78.3 vs 602.1 +/- 69.6 pg/mL), P = NS. However, despite similar peak exercise norepinephrine levels (2735.8 +/- 320.1 vs 2403.1 +/- 371.6 pg/mL), heart rate at peak exercise was higher in subjects receiving carvedilol (135 +/- 4 bpm) than those receiving metoprolol XL (117 +/- 6 bpm), P = 0.02. Similar norepinephrine release and more complete beta 1-blockade is observed in well-matched subjects with chronic heart failure treated with a mean daily dose of metoprolol XL 96.4 mg compared with carvedilol 32.9 mg

BACKGROUND: Chronotropic incompetence (CI) is often seen in subjects with chronic congestive heart failure (CHF). The prevalence of CI, its mechanisms and association with beta-blocker use as well as exercise capacity have not been clearly defined. METHODS AND RESULTS: Cardiopulmonary exercise tolerance testing data for 278 consecutive patients with systolic CHF was analyzed. CI, defined as the inability to reach 80% of maximally predicted heart rate was present in 128 of 278 subjects (46%). The prevalence of CI was highest in those with most impaired exercise capacity (72, 48, and 24% for subjects with a VO(2) of <14.0, 14.0-20.0, and >20.0 ml/kg/min respectively; p=0.001). While subjects with CI had lower peak exercise heart rate (114 vs. 152 bpm), and lower peak VO(2) (15.4 vs. 19.9 ml/kg/min), they were equally likely to be on chronic beta-blocker therapy (74% vs. 71%; p=0.51). Heart rate and norepinephrine (NE) levels were measured during exercise in a separate cohort of 24 subjects with CHF. There was no difference in beta-blocker dose between subjects with and without CI, however, exercise induced NE release and Chronotropic Responsiveness Index, a measure of post-synaptic beta-receptor sensitivity to NE, were lower in subjects with CI (1687+/-911 vs. 2593+/-1451 pg/ml p=0.08; CRI 12.7+/-5.7 vs. 22.1+/-4.7, p=0.002). CONCLUSIONS: CI occurs in >70% of subjects with advanced systolic CHF irrespective of beta-blocker use and is associated with a trend toward impaired NE release, post-synaptic beta-receptor desensitization and reduced exercise capacity

INTRODUCTION: Previous animal studies of chronic heart failure (CHF) suggest that angiotensin-converting enzyme (ACE) inhibitors of differing tissue avidity provide varying levels of renin-angiotensin system (RAS) suppression. Human studies have not consistently confirmed these animal findings. We hypothesised that production of circulating aldosterone (ALDO) would be suppressed to a greater extent in subjects treated with an ACE-inhibitor of higher tissue avidity. We randomised subjects with stable CHF to receive the low-tissue affinity ACE-inhibitor enalapril (ENAL) or the high-tissue affinity ACE-inhibitor trandolapril (TRAN), and assessed circulating ALDO levels at baseline and after eight weeks of treatment. METHODS: Thirty clinically stable subjects with CHF and left ventricular ejection fraction (LVEF) < 40% who were in a steady-state fluid balance were enrolled into a prospective, randomised double-blind trial. After a one month run-in period for standardisation to initial ACE-inhibition with ENAL, baseline circulating ALDO levels were measured and patients were randomised to receive ENAL 40 mg versus TRAN 4 mg (or the maximally tolerated doses) for eight weeks. Final determination of ALDO levels were made at the end of the 8-week study period. RESULTS: Baseline clinical characteristics including age, diabetes, LVEF, serum sodium, potassium and creatinine concentrations, and background medications were similar in both groups. We found no statistically significant difference in circulating ALDO levels between the ENAL and TRAN groups at the end of the 8-week study period. [ENAL (12.6 vs. 13.3 ng/dL); TRAN (12.5 vs. 14.5 ng/dL); p=NS]. CONCLUSION: We found no statistically significant difference in circulating ALDO levels between high- and low-tissue affinity ACE-inhibitor therapy. Further studies assessing ALDO production at the tissue level is warranted.

BACKGROUND: Oxidative stress is an important pathophysiologic feature in chronic heart failure (CHF) and may in part result from the inability to counteract acute surges of circulating oxidant products. Oxidized low-density lipoprotein (oxLDL) is an emerging prognostic marker in CHF. Accordingly, we investigated the effect of exercise-induced oxidative stress on circulating levels of oxLDL and its association with clinical outcomes in CHF. METHODS AND RESULTS: Plasma levels of oxLDL and low-density lipoprotein cholesterol (LDL-c) were measured at rest and after maximal exercise in 48 subjects with CHF and 12 healthy controls. Subjects with CHF had a higher baseline oxLDL (77.7 +/- 3.2 U/L vs 57.9 +/- 5.0 U/L, P = .01) and a higher baseline oxLDL/LDL-c ratio (0.87 +/- 0.04 vs 0.49 +/- 0.04, P < or = .001). Exercise induced an increase in oxLDL in subjects with CHF (77.7 +/- 3.2 U/L to 85.3 +/- 3.0 U/L, P < or = .001) but not in controls (57.9 +/- 5.0 to 61.4 +/- 5.5, P = .17). In 39 subjects for whom follow-up data were available, an increase in oxLDL of more than 11.0 U/L was associated with an increased risk to meet a combined end point of death and need for ventricular assist device or heart transplant during a 19-month follow-up period (hazard ratio 8.6; 95% confidence interval 1.0-73.8, P = .05); this remained significant when adjusted for peak oxygen consumption, left ventricular ejection fraction, New York Heart Association class, sex, and age (hazard ratio 46.6, 95% confidence interval 1.5-1438.1, P = .02). CONCLUSION: Plasma oxLDL and the oxLDL/LDL-c ratio are elevated in subjects with CHF. Whether assessment of oxLDL during maximal exercise allows early identification of subjects at highest risk for adverse outcomes should be systematically investigated.

Chronic heart failure (CHF) has become an epidemic in the United States, with approximately 550,000 new cases annually. With the evolution of pharmacotherapy targeting neurohormonal pathways, the annual mortality in subjects with New York Heart Association (NYHA) class IV CHF has dramatically improved from 52% in the seminal CONSENSUS trial to less than 20% in more recent trials. Suppression of the renin-angiotensin-aldosterone system remains the first line of neurohormonal blockade followed by the addition of selective beta-adrenoreceptor blockers. For patients with NYHA class I and II symptoms, mortality rates have decreased to approximately 5% or less per year with the use of angiotensin-converting enzyme inhibitors, beta-blockers and aldosterone receptor blockers. However, after achieving optimal doses of the indicated pharmacotherapy, and despite the additional benefits obtained with biventricular pacemakers, there are still many patients who continue to experience signs and symptoms of CHF. Recognizing the beneficial effects of the above treatments on left ventricular (LV) remodeling, strategies have been developed to surgically reshape the left ventricle in patients with LV dilation who have associated poor LV function. This review will discuss the techniques and recent developments regarding surgical reshaping of the dilated, dysfunctional, and remodeled left ventricle