John E. Brush

Abnormal Endothelium-Dependent Vascular Relaxation in Patients with Essential Hypertension

BACKGROUND Endothelium regulates vascular tone by influencing the contractile activity of vascular smooth muscle. This regulatory effect of the endothelium on blood vessels has been shown to be impaired in atherosclerotic arteries in humans and animals and in animal models of hypertension. METHODS To determine whether patients with essential hypertension have an endothelium-dependent abnormality in vascular relaxation, we studied the response of the forearm vasculature to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct dilator of smooth muscle) in 18 hypertensive patients (mean age [+/- SD], 50.7 +/- 10 years; 10 men and 8 women) two weeks after the withdrawal of antihypertensive medications and in 18 normal controls (mean age, 49.9 +/- 9; 9 men and 9 women). The drugs were infused at increasing concentrations into the brachial artery, and the response in forearm blood flow was measured by strain-gauge plethysmography. RESULTS The basal forearm blood flow was similar in the patients and controls (mean +/- SD, 3.4 +/- 1.3 and 3.7 +/- 0.8 ml per minute per 100 ml of forearm tissue, respectively; P not significant). The responses of blood flow and vascular resistance to acetylcholine were significantly reduced in the hypertensive patients (P less than 0.0001); maximal forearm flow was 9.1 +/- 5 ml per minute per 100 ml in the patients and 20.0 +/- 8 ml per minute per 100 ml in the controls (P less than 0.0002). However, there were no significant differences between groups in the responses of blood flow and vascular resistance to sodium nitroprusside. Because the vasodilator effect of acetylcholine might also be due to presynaptic inhibition of the release of norepinephrine by adrenergic nerve terminals, the effect of acetylcholine was assessed during phentolamine-induced alpha-adrenergic blockade. Under these conditions, it was also evident that the responses to acetylcholine were significantly blunted in the hypertensive patients (P less than 0.03). CONCLUSIONS Endothelium-mediated vasodilation is impaired in patients with essential hypertension. This defect may play an important part in the functional abnormalities of resistance vessels that are observed in hypertensive patients.

Angina Due to Coronary Microvascular Disease in Hypertensive Patients without Left Ventricular Hypertrophy

When angina occurs in patients with hypertension, it is usually attributed to coronary artery disease or left ventricular hypertrophy. To determine the contribution of coronary microvascular abnormalities to angina in patients with hypertension, we evaluated hypertensive patients without coronary artery disease or left ventricular hypertrophy by measuring the coronary responses to rapid atrial pacing before and after administration of ergonovine. We compared 12 hypertensive patients who had pacing-induced angina with 13 normotensive subjects without such angina. The two groups had similar coronary flow (in the great cardiac vein) at rest; however, pacing increased coronary flow less in hypertensive patients with angina than in normotensive subjects (48 vs. 83 percent; P = 0.05). In the hypertensive patients with angina, pacing after ergonovine increased coronary flow by only 32 percent (as compared with 48 percent before ergonovine; P less than 0.05) and decreased coronary resistance by 15 percent (as compared with 28 percent before ergonovine; P less than 0.05), indicating the presence of ergonovine-induced vasoconstriction. In normotensive subjects, in contrast, cardiac pacing after ergonovine increased coronary flow by 112 percent (P less than 0.001), and its effect on coronary resistance was not different from that of pacing before ergonovine. The hypertensive patients with angina had a significant increase in myocardial oxygen extraction during pacing after ergonovine and less of an increase in myocardial lactate consumption - a response consistent with the presence of myocardial ischemia. Thus, angina in hypertensive patients without epicardial coronary disease may be caused by myocardial ischemia, which appears to be due to an abnormally elevated resistance of the coronary microvasculature.

Use of the initial electrocardiogram to predict in-hospital complications of acute myocardial infarction.

Abstract We evaluated the initial electrocardiogram as a predictor of complications in 469 patients with suspected acute myocardial infarction. An electrocardiogram was classified as positive if it showed one or more of the following: evidence of infarction, ischemia, or strain; left ventricular hypertrophy; left bundle-branch block; or paced rhythm. Forty-two (14 per cent) of 302 patients with positive electrocardiograms had at least one life-threatening complication (ventricular fibrillation, sustained ventricular tachycardia, or heart block), as compared with 1 (0.6 per cent) of 167 patients with a negative electrocardiogram. Life-threatening complications were therefore 23 times more likely if the initial electrocardiogram was positive (P<0.001). Other complications were 3 to 10 times more likely (P<0.01), interventions were 4 to 10 times more likely (P<0.05), and death was 17 times more likely (P<0.001) in patients with a positive electrocardiogram. We conclude that patients with a negative initial e...

A Campaign to Improve the Timeliness of Primary Percutaneous Coronary Intervention : Door-to-Balloon: An Alliance for Quality

OBJECTIVES We sought to describe the rationale and methods for Door-to-Balloon (D2B): An Alliance for Quality, an international effort organized by the American College of Cardiology in partnership with the American Heart Association and 37 other organizations to rapidly translate research about how best to achieve outstanding D2B times for patients with ST-segment elevation myocardial infarction (STEMI) into practice. BACKGROUND The D2B time, the time between hospital arrival and primary percutaneous coronary intervention for patients with STEMI, is strongly associated with the likelihood of survival, yet the majority of patients are not treated within the guideline-recommended time of </=90 min. Recent research has revealed key and underused strategies that are associated with achieving faster D2B times. METHODS The D2B Alliance has enrolled approximately 1,000 hospitals. Its goal is to achieve a D2B time of </=90 min for at least 75% of non-transferred patients. The key strategies chosen by the D2B Alliance include having the emergency medicine physician activate the catheterization laboratory with a single call, having the team prepared within 20 to 30 min of the call; rapid data feedback; a team-based approach; and administrative support. The use of a pre-hospital electrocardiogram by emergency medical services personnel to activate the catheterization laboratory was also noted as an additional optional strategy. The project has many approaches to promote participation and adoption of effective strategies. An evaluation component is also described. CONCLUSIONS The design of the D2B: An Alliance for Quality, a novel campaign to improve D2B time, is described.

Left ventricular hypertrophy and impaired diastolic filling in essential hypertension. Diastolic mechanisms for systolic dysfunction during exercise.

Left ventricular ejection fraction is normal at rest but may respond abnormally to exercise in many patients with essential hypertension. To assess the determinants of the abnormal ejection fraction response to exercise, we performed radionuclide angiography at rest and during exercise in 41 hypertensive patients without coronary artery disease. In 22 patients (group 1), the ejection fraction increased more than 5% during exercise; in the other 19 patients (group 2), the ejection fraction either increased by less than 5% or decreased with exercise. Left ventricular diastolic filling was impaired at rest in patients in group 2 compared with group 1, with reduced peak filling rate (2.5 +/- 0.4 vs. 3.1 +/- 0.7 end-diastolic volume/sec; p less than 0.01) and prolonged time to peak filling rate (175 +/- 28 vs. 153 +/- 22 msec; p less than 0.01). Impaired diastolic filling in group 2 was associated with less augmentation in end-diastolic volume during exercise compared with group 1 (p less than 0.01). These observations were not dependent on the threshold value that was arbitrarily chosen to define an abnormal ejection fraction response, as there were significant correlations for the entire group between the magnitude of change in ejection fraction with exercise and both the resting peak filling rate (r = 0.46) and the change in end-diastolic volume with exercise (r = 0.62).(ABSTRACT TRUNCATED AT 250 WORDS)

National Efforts to Improve Door-to-Balloon Time. Results From the Door-to-Balloon Alliance

OBJECTIVES The purpose of this study was to determine if enrollment in the Door-to-Balloon (D2B) Alliance, a national quality campaign sponsored by the American College of Cardiology and 38 partner organizations, was associated with increased likelihood of patients who received primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI) being treated within 90 min of hospital presentation. BACKGROUND The D2B Alliance, launched in November 2006, sought to achieve the goal of having 75% of patients with STEMI treated within 90 min of hospital presentation. METHODS We conducted a longitudinal study of D2B times in 831 hospitals participating in the National Cardiovascular Data Registry (NCDR) CathPCI Registry, April 1, 2005, to March 31, 2008. RESULTS By March 2008, >75% of patients had D2B times of < or = 90 min, compared with only about one-half of patients with D2B times within 90 min in April 2005. Trends since the launch of the D2B Alliance showed that patients treated in hospitals enrolled in the D2B Alliance for at least 3 months were significantly more likely than patients treated in nonenrolled hospitals to have D2B times within 90 min, although the magnitude of the difference was modest (odds ratio: 1.16; 95% confidence interval: 1.07 to 1.27). CONCLUSIONS The D2B Alliance reached its goal of 75% of patients with STEMI having D2B times within 90 min by 2008.

In vivo measurement of neuronal uptake of norepinephrine in the human heart.

Neuronal uptake (Uptake-1) of the sympathetic neurotransmitter norepinephrine from the circulation in the human heart was assessed in vivo with three techniques. 1) Cardiac removal of intravenously infused tracer-labeled norepinephrine was measured before and after Uptake-1 blockade with desipramine; 2) the difference between the fractional extraction of radioactive norepinephrine and of radioactive isoproterenol, which is not a substrate for neuronal uptake, was used to estimate the removal of norepinephrine by Uptake-1 in the heart compared with other vascular beds (arm, leg, brain, and lungs); and 3) regional arteriovenous differences in radioactive and endogenous dihydroxyphenylglycol (DHPG), an exclusively intraneuronal metabolite of norepinephrine, were compared in these beds. In untreated patients, cardiac removal of radioactive norepinephrine averaged 79%, whereas in desipramine-treated patients, cardiac removal of radioactive norepinephrine averaged 19%, a value similar to that of isoproterenol in untreated patients (14%), confirming that in the heart the non-neuronal removals of isoproterenol and norepinephrine were similar. In the heart, 69% of delivered norepinephrine was estimated to be removed by Uptake-1, a much higher percentage than that in the arm (14%), leg (7%), brain (10%), and lungs (4%). The cardiac arteriovenous increment in endogenous DHPG (137%) far exceeded that of the other beds (49%, 26%, 39%, and -19%, respectively), and radioactive DHPG in the great cardiac vein exceeded arterial levels by 113%, whereas in the other beds, arterial radioactive DHPG exceeded venous levels. The results indicate that the human heart is exceptionally dependent on neuronal uptake for in vivo removal of circulating norepinephrine.

Relation between door-to-balloon times and mortality after primary percutaneous coronary intervention over time: a retrospective study

BACKGROUND Recent reductions in average door-to-balloon (D2B) times have not been associated with decreases in mortality at the population level. We investigated this seemingly paradoxical finding by assessing components of this association at the individual and population levels simultaneously. We postulated that the changing population of patients undergoing primary percutaneous coronary intervention (pPCI) contributed to secular trends toward an increasing mortality risk, despite consistently decreased mortality in individual patients with shorter D2B times. METHODS This was a retrospective study of ST-elevation myocardial infarction (STEMI) patients who underwent pPCI between Jan 1, 2005, and Dec 31, 2011, in the National Cardiovascular Data Registry (NCDR) CathPCI Registry. We looked for catheterisation laboratory visits associated with STEMI. We excluded patients not undergoing pPCI, transfer patients for pPCI, patients with D2B times less than 15 min or more than 3 h, and patients at hospitals that did not consistently report data across the study period. We assessed in-hospital mortality in the entire cohort and 6-month mortality in elderly patients aged 65 years or older matched to data from the Centers for Medicare and Medicaid Services. We built multilevel models to assess the relation between D2B time and in-hospital and 6-month mortality, including both individual and population-level components of this association after adjusting for patient and procedural factors. FINDINGS 423 hospitals reported data on 150,116 procedures with a 55% increase in the number of patients undergoing pPCI at these facilities over time, as well as many changes in patient and procedural factors. Annual D2B times decreased significantly from a median of 86 min (IQR 65-109) in 2005 to 63 min (IQR 47-80) in 2011 (p<0·0001) with a concurrent rise in risk-adjusted in-hospital mortality (from 4·7% to 5·3%; p=0·06) and risk-adjusted 6-month mortality (from 12·9% to 14·4%; p=0·001). In multilevel models, shorter patient-specific D2B times were consistently associated at the individual level with lower in-hospital mortality (adjusted OR for each 10 min decrease 0·92; 95% CI 0·91-0·93; p<0·0001) and 6-month mortality (adjusted OR for each 10 min decrease, 0·94; 95% CI 0·93-0·95; p<0·0001). By contrast, risk-adjusted in-hospital and 6-month mortality at the population level, independent of patient-specific D2B times, rose in the growing and changing population of patients undergoing pPCI during the study period. INTERPRETATION Shorter patient-specific D2B times were consistently associated with lower mortality over time, whereas secular trends suggest increased mortality risk in the growing and changing pPCI population. The absence of association of annual D2B time and changes in mortality at the population level should not be interpreted as an indication of its individual-level relation in patients with STEMI undergoing primary PCI. FUNDING National Heart, Lung, and Blood Institute.

ACCF/AHA/SCAI 2013 Update of the Clinical Competence Statement on Coronary Artery Interventional Procedures A Report of the American College of Cardiology Foundation/American Heart Association/American College of Physicians Task Force on Clinical Competence and Training (Writing Committee to Revise the 2007 Clinical Competence Statement on Cardiac Interventional Procedures)

Granting clinical staff privileges to physicians is the primary mechanism institutions use to uphold quality care. The Joint Commission requires that medical staff privileges be based on professional criteria specified in medical staff bylaws. Physicians themselves are charged with defining the

Cardiac norepinephrine kinetics in hypertrophic cardiomyopathy.

We examined the uptake and release of norepinephrine in the cardiac circulation and other regional vascular beds in 11 patients with hypertrophic cardiomyopathy (HCM) and in 10 control subjects during simultaneous infusion of tracer-labeled norepinephrine and isoproterenol. Cardiac neuronal uptake of norepinephrine was assessed by comparing regional removal of tracer-labeled norepinephrine with that of tracer-labeled isoproterenol (which is not a substrate for neuronal uptake) and by the relation between production of dihydroxyphenylglycol (DHPG), an exclusively intraneuronal metabolite of norepinephrine, and regional spillover of norepinephrine. Cardiac extraction of norepinephrine averaged 59 +/- 17% in the patients with HCM, significantly less than in the control subjects (79 +/- 13%, p less than 0.05), whereas cardiac extraction of isoproterenol was similar in the two groups (13 +/- 23% versus 13 +/- 14%), indicating that neuronal uptake of norepinephrine was decreased in the patients with HCM. The cardiac arteriovenous difference in norepinephrine was significantly larger in the patients with HCM than in the control subjects (73 +/- 77 versus 13 +/- 50 pg/ml, p less than 0.05), as was the product of the arteriovenous difference in norepinephrine and coronary blood flow (7.3 +/- 7.3 versus 0.8 +/- 3.0 ng/min, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)