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Although the syndrome of heart failure with preserved systolic function may occur in up to 40% of all heart failure patients, the clinical, angiographic characteristics, and long-term outcomes of these patients are poorly understood. We prospectively evaluated 2,498 consecutive patients with New York Heart Association class II to IV symptoms and ejection fractions of >40%, who underwent cardiac catheterization between January 1984 and December 1996 at Duke University Medical Center. The median age for the entire cohort was 63 years; 25% of the population was >71 years old. In addition, 55% of the patients were women, 65% had ischemic heart disease, 28% had a history of diabetes, and 62% had a history of hypertension. The median ejection fraction was 58%. One third of the patients had multivessel disease by coronary angiography. The overall 5-year mortality of the total population was 28%. The independent predictors of mortality (p <0.05) using a multivariable Cox proportional hazard model were age, class IV symptoms, ejection fraction, coronary artery disease index, diabetes, peripheral vascular disease, and minority ethnic group. Heart failure with preserved systolic function is characterized by unique clinical and angiographic characteristics associated with a 5-year mortality rate of 28%. Furthermore, several clinical and angiographic characteristics are predictive of long-term survival. [ABSTRACT FROM AUTHOR]

P-selectin is an important marker of platelet activation and may be up-regulated in patients with congestive heart failure (CHF). We sought to prospectively compare simultaneously determined platelet and soluble P-selectin in patients with CHF and in healthy controls. Matched soluble levels by enzyme-linked immmunosorbent assay, and platelet-bound expression by whole blood flow cytometry of P-selectin were measured in 22 patients with CHF and compared with 14 healthy controls. Twelve patients were aspirin free and 10 patients were taking aspirin (81 to 500 mg/day). Patients with CHF had significantly elevated soluble P-selectin (186.6 +/- 82.7 ng/ml, p = 0.017) and more than twofold increased expression of platelet-bound P-selectin (9.58 +/- 7.16% of positive platelets, p = 0.021) compared with the P-selectin profile (102.6 +/- 29.0 ng/ml of plasma, and 4.06 +/- 1.21% of positive platelets, respectively) in controls. Aspirin therapy did not affect the P-selectin profile in patients with CHF. Despite antecedent aspirin therapy and interindividual variability of the P-selectin profile, soluble and platelet P-selectin were elevated in most patients with severe CHF, suggesting persistent platelet activation. [ABSTRACT FROM AUTHOR]

Depression is common in patients with heart failure (HF), prognostic for adverse outcomes and purportedly related to disease severity. Psychological and physiologic factors relevant to HF were assessed in HF-ACTION, a large randomized study of aerobic exercise training in patients with systolic HF. The relation of objective and subjective parameters was compared with scores on the Beck Depression Inventory (BDI) to examine the hypothesis that depressive symptoms are better associated with perception of disease severity than with objective markers of HF severity. At baseline, 2,322 of 2,331 subjects entered into HF-ACTION completed questionnaires to assess depression (BDI) and quality of life (Kansas City Cardiomyopathy Questionnaire [KCCQ]). Objective markers of HF severity included ejection fraction, B-type natriuretic peptide, and peak oxygen consumption (using cardiopulmonary exercise testing, with evaluation of duration and respiratory exchange ratio also performed). Measures more likely to be affected by perceived functional status included New York Heart Association (NYHA) classification and the 6-minute walk test. Objective assessments of disease severity were slightly related (peak oxygen consumption) or not related (B-type natriuretic peptide and ejection fraction) to BDI scores. Using multivariate analysis (KCCQ not included), only age, gender, cardiopulmonary exercise testing duration, NYHA class, 6-minute walk distance, and peak respiratory exchange ratio independently correlated with BDI scores. In conclusion, depression was minimally related to objective assessments of severity of disease in patients with HF, but was associated with patient (and clinician) perceptions of disease severity. Addressing depression might improve symptoms in patients with HF. [ABSTRACT FROM AUTHOR]

This study examined the effects of exercise and stress management training on clinical outcomes and medical expenditures over a 5-year follow-up period in 94 male patients with established coronary artery disease (CAD) and evidence of ambulatory or mental stress-induced myocardial ischemia. Patients were randomly assigned to 4 months of aerobic exercise 3 times per week or to a 1.5-hour weekly class on stress management; patients who lived too far from Duke to participate in the weekly treatments formed the usual care control group. Follow-up was performed at the end of treatment and annually thereafter for 5 years. Stress management was associated with a significant reduction in clinical CAD events relative to usual care over each of the first 2 years of follow-up and after 5 years. Economic analyses revealed that stress management was associated with lower medical costs than usual care and exercise in the first 2 years, and that the cumulative cost over 5 years was also lower for stress management relative to usual care. These results suggest that there may be clinical and economic benefit to offering the type of preventive stress management and exercise interventions provided to patients with myocardial ischemia. Moreover, these findings suggest that the financial benefits that accrue from an appropriately targeted intervention may be substantial and immediate. [ABSTRACT FROM AUTHOR]

Clinicians have relied on history and results from physical examinations to guide treatment of patients with advanced congestive heart failure, but these results may not reflect disease severity or hemodynamic status. We assessed how the distance walked in 6 minutes relates to clinical outcomes and symptoms of such patients. We compared the rates of death, hospitalization, and their composite at 1 year by the distance walked in 6 minutes at baseline and at 1 month, and by the change in distance between baseline and 1 month in 440 patients enrolled in a randomized trial. We also assessed the relations of baseline distance walked to symptom score and New York Heart Association class. The median distance increased from 218 m at baseline to 280 m at 1 month. Of 365 patients able to perform the baseline walk, 121 (33%) died and 217 (60%) were hospitalized compared with 46 (61%) and 34 (45%) of 75 patients unable to walk at baseline. Baseline distance significantly predicted mortality (hazard ratio 0.58/100-m increase, 95% confidence interval 0.50 to 0.68, p <0.001), even after adjustment. Baseline distance also significantly predicted hospitalization and the composite end point, as did the 1-month distance walked. The change in distance walked from baseline to 1 month did not predict any end point. Baseline distance correlated only moderately with symptom score (r = -0.385, p <0.001) and New York Heart Association class (r = -0.468, p <0.001). Distance walked during 6 minutes independently and strongly predicts mortality and hospitalization in patients with advanced congestive heart failure. This may be a simple, noninvasive, objective way to risk-stratify these patients and standardize their treatment. [ABSTRACT FROM AUTHOR]

The Coumadin Aspirin Reinfarction Study demonstrated that combination treatment with fixed dose warfarin (1 or 3 mg) + aspirin 80 mg was not superior to aspirin 160 mg alone after myocardial infarction for reducing nonfatal reinfarction, nonfatal stroke, and cardiovascular death. In this analysis, we examined the importance of aspirin dose in the protection against the secondary end point of ischemic stroke. The comparison arms for this analysis were warfarin 1 mg + aspirin 80 mg versus aspirin 160 mg. In the Coumadin Aspirin Reinfarction Study, 2,028 patients were randomized to aspirin 80 mg plus warfarin 1 mg, and 3,393 were randomized to aspirin 160 mg alone. A predictive model for ischemic stroke was developed using the Cox proportional-hazards model. A reduced Cox proportional-hazards model was developed to test for the effect of aspirin dose on ischemic stroke in predefined subgroups. The incidence of ischemic stroke was lower in patients treated with aspirin 160 mg than in patients treated with aspirin 80 mg + warfarin 1 mg (0.6% vs 1.1%; p = 0.0534). Age, previous stroke or transient ischemic attack, and aspirin dose were independent predictors of ischemic stroke. In addition, the highest risk patients, those with Q-wave myocardial infarction and male patients, appeared to receive greater benefit from aspirin 160 mg than from aspirin 80 mg + warfarin 1 mg. The results of this secondary analysis suggest that aspirin 160 mg is more effective than aspirin 80 mg + warfarin 1 mg in preventing ischemic stroke in post-myocardial infarction patients. [ABSTRACT FROM AUTHOR]

Pre- and post-treatment platelet and soluble P-selectin were measured in a group of patients enrolled in the GUSTO-III study and were correlated with clinical outcomes. A peak in soluble P-selectin levels at 3 hours after thrombolytic therapy and lower baseline platelet P-selectin were associated with successful thrombolysis. [ABSTRACT FROM AUTHOR]

There is substantial clinical evidence that the incidence of depression and mortality after acute coronary events are strongly related. As mediators of coronary thrombosis, platelets may represent a link between these events, and could be possibly targeted by therapy with serotonin reuptake inhibitors. [ABSTRACT FROM AUTHOR]

Investigations of calcium antagonists in patients with advanced heart failure have raised concern over an increased risk of worsening heart failure and heart failure deaths. We assessed the effect of amlodipine on cause-specific mortality in such patients enrolled in a randomized, double-blind, placebo-controlled trial. In total, 1,153 patients in New York Heart Association class IIIb or IV heart failure were randomized to receive amlodipine or placebo, along with angiotensin-converting enzyme inhibitors, diuretics, and digitalis. Over a median 14.5 months of follow-up, 413 patients died. Cardiovascular deaths accounted for 89% of fatalities, 50% of which were sudden deaths and 45% of which were due to pump failure, with fewer attributed to myocardial infarction (3.3%) or other cardiovascular causes (1.6%). Amlodipine treatment resulted in a greater relative reduction in sudden deaths (21%) than in pump failure deaths (6.6%) overall. When patients were classified by etiology of heart failure (ischemic or nonischemic), cause-specific mortality did not differ significantly between treatment groups in the ischemic stratum. In the nonischemic stratum, however, sudden deaths and pump failure deaths were reduced by 38% and 45%, respectively, with amlodipine. Thus, when added to digitalis, diuretics, and angiotensin-converting enzyme inhibitors in patients with advanced heart failure, amlodipine appears to have no effect on cause-specific mortality in ischemic cardiomyopathy, but both pump failure and sudden deaths appear to be decreased in nonischemic heart failure patients treated with amlodipine. [ABSTRACT FROM AUTHOR]

We performed a multicenter, open-label study to determine the long-term safety and efficacy of a new extended-release once-a-night niacin preparation, Niaspan, in the treatment of hypercholesterolemia. Niaspan, 0.5 to 3.0 g once a night at bedtime, was used alone or in combination with a statin (inhibitor of hydroxymethylglutaryl coenzyme A reductase), a bile acid sequestrant, or both. Patients included 269 hypercholesterolemic male and female adults enrolled in a 96-week study, and 230 additional adults for whom short-term safety data were available. The dosages of Niaspan attained by 269 patients were 1,000 mg (95% of patients), 1,500 mg (86%), and 2,000 mg (65%). After 48 weeks of treatment, Niaspan alone (median dose 2,000 mg) reduced low-density lipaprotein (LDL) cholesterol (18%), apolipoprotein B (15%), total cholesterol (11%), triglycerides (24%), and lipoprotein(a) (36%), and increased high-density lipoprotein (HDL) cholesterol (29%). Niaspan plus a statin lowered LDL cholesterol (32%), apolipoprotein B (26%), total cholesterol (23%), triglycerides (30%), and lipoprotein(a) (19%), and increased HDL cholesterol (26%). Reversible elevations of aspartate aminotransferase or alanine aminotransferase more than twice the normal range occurred in 2.6% of patients. One patient discontinued Niaspan because of transaminase elevations. Intolerance to flushing, leading to discontinuation of Niaspan, occurred in 4.8% of patients. The overall rate of discontinuance due to flushing in this study combined with 2 previous randomized trials was 7.3%. In the long-term treatment of hypercholesterolemia, Niaspan produced favorable changes in LDL and HDL cholesterol, triglycerides, and lipoprotein(a). Adverse hepatic effects were minor and occurred at rates similar to those reported for statin therapy. [ABSTRACT FROM AUTHOR]

Studies the effect of selective serotonin reuptake inhibitors (SSRI) on platelets in patients with coronary artery disease. Study methods and subjects; Importance of SSRI in the survival of patients after ischemic events; Association of chronic SSRI therapy with a broad-spectrum inhibition of various platelet characteristics.

Angina pectoris (AP) has different prognostic implications in various populations. Patients with diabetes mellitus (DM) may experience neuropathy such that AP may not be perceived in the setting of coronary artery disease (CAD). The prognostic utility of AP in DM patients with CAD is not well known. We analyzed patients with CAD who underwent coronary angiography at Duke University from 2002 to 2011 and compared patients with and without AP within the previous 6 weeks stratified by DM status. We used multivariable Cox regression to assess the association between AP and the outcomes of cardiovascular (CV) hospitalization/revascularization, all-cause mortality/myocardial infarction/revascularization, and all-cause mortality. Of 17,211 patients with CAD, 5,284 (31%) had DM and AP was present in 69% of DM and 67% of non-DM. After risk adjustment, the risk of CV hospitalization/revascularization and all-cause mortality/myocardial infarction/revascularization in patients with and without AP was similar regardless of DM status (all p ≥0.05). In patients with or without DM, AP was associated with lower all-cause mortality compared with no AP (adjusted hazard ratio 0.89, 95% confidence interval 0.82 to 0.97, p = 0.005 for DM patients). The relation between AP status and clinical outcomes was not dependent on DM status (all interaction p >0.10). In conclusion, in patients with CAD, AP was associated with similar risk for CV hospitalization and revascularization and lower all-cause mortality compared with patients without AP regardless of DM status. Future studies are needed to assess whether these findings are related to increased severity of disease in those without AP or whether AP leads to differential management that improves survival., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In 1,009 patients with atrial fibrillation and congestive heart failure, the 2-year mortality rate was 31% in patients treated with rate control (n = 505) versus 29% in patients treated with rhythm control (n = 504). After adjusting for differences in baseline characteristics and medications, no significant difference in mortality was found between the 2 groups.

We analyzed heart rate variability from normal RR intervals in patients with advanced congestive heart failure. Although most patients had decreased HRV, patients with a life-threatening cardiac event or death (n = 8) within 18 months had significantly lower heart rate variability than those who did not (n = 18), which may have value in determining prognosis in this population.

We reviewed the records of 242 patients admitted over 1 year with heart failure and an ejection fraction < or = 45% to assess the use of angiotensin-converting enzyme inhibitors. Most patients were treated with angiotensin-converting enzyme inhibitors. However, an important minority (8%) had no apparent reason for the lack of this treatment, highlighting the need for strategies to increase the use of these beneficial agents.

Previous research has established that patients with coronary artery disease (CAD) have an increased risk of death if they are depressed at the time of hospitalization. Follow-up periods have been short in these studies; therefore, the present investigation examined this phenomenon over an extended period of time. Patients with established CAD (n = 1,250) were assessed for depression with the Zung Self-Rating Depression Scale (SDS) and followed for subsequent mortality. Follow-up ranged up to 19.4 years. SDS scores were associated with increased risk of subsequent cardiac death (p = 0.002) and total mortality (p < 0.001) after controlling for initial disease severity and treatment. Patients with moderate to severe depression had a 69% greater odds of cardiac death and a 78% greater odds of mortality from all causes than nondepressed patients. Increased risk was not confined to the initial months after hospitalization. Patients with high SDS scores at baseline still had a higher risk of cardiac death > 5 years later (p < 0.005). Compared with the nondepressed, patients with moderate to severe depression had an 84% greater risk 5 to 10 years later and a 72% greater risk after > 10 years. Patients with mild depression had intermediate levels of risk in all models. The heightened long-term risk of depressed patients suggests that depression may be persistent or frequently recurrent in CAD patients and is associated with CAD progression, triggering of acute events, or both.

The focus of new research efforts to improve the morbidity and mortality associated with acute myocardial infarction (AMI) has turned to adjuvant agents that show promise of improving outcomes following coronary thrombolysis. We enrolled 162 patients with AMI in a randomized trial comparing front-loaded tissue-plasminogen activator (t-PA) plus weight-adjusted heparin with anisoylated plasminogen streptokinase activator complex (APSAC) without heparin as well as standard-dose (325 mg) and low-dose (81 mg) aspirin. The primary end point was an in-hospital morbidity profile; secondary end points were clinical and angiographic potency and hemorrhagic events. Selected sites performed an electrocardiographic substudy to determine the time to 50% ST-segment recovery and the time to steady state. Although the trial was terminated when the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries-I trial showed that t-PA had a significant mortality advantage over streptokinase, important trends were evident. Patients given t-PA and heparin were better anticoagulated (p = 0.001), yet AP-SAC-treated patients had more bleeding complications. The primary end point favored t-PA (25.4% vs 31.3%), and the secondary end points were similar in both groups. In the electrocardiographic substudy, the t-PA group achieved both 50% ST-segment recovery and steady-state recovery sooner than the APSAC group. Patients taking low-dose aspirin had lower in-hospital mortality and less recurrent ischemia but more strokes than the standard-dose aspirin group. Thus, this trial demonstrated trends favoring front-loaded t-PA with weight-adjusted heparin over APSAC without heparin in the treatment of AMI. The use of low-dose aspirin did not appear to impose a loss of protection from adverse events, nor did standard-dose aspirin increase serious bleeding.

Intravenous heparin is routinely given after thrombolytic therapy for patients with acute myocardial infarction in the United States and in some, but by no means all, other countries. Several trials have documented improved infarct-artery patency in patients treated with heparin; however, none was large enough individually to assess the effect of heparin on clinical outcomes. We performed a systematic overview of the 6 randomized controlled trials (1,735 patients) to summarize the available data concerning the risks and benefits of intravenous heparin versus no heparin after thrombolytic therapy. Mortality before hospital discharge was 5.1% for patients allocated to intravenous heparin compared with 5.6% for controls (relative risk reduction of 9%, odds ratio 0.91, 95% confidence interval 0.59 to 1.39). Similar rates of recurrent ischemia and reinfarction were observed among those allocated to heparin therapy or control. The rates of total stroke, intracranial hemorrhage, and severe bleeding were similar in patients allocated to heparin; however, the risk of any severity of bleeding was significantly higher (22.7% vs 16.2%; odds ratio 1.55, 95% confidence interval 1.21 to 1.98). There was no significant difference in the observed effects of heparin between patients receiving tissue-type plasminogen activator and those receiving streptokinase or anisoylated plasminogen streptokinase activator complex, or between patients who did and did not receive aspirin. The findings of this overview demonstrate that insufficient clinical outcome data are available to support or to refute the routine use of intravenous heparin therapy after thrombolysis. It is not known if these findings are due to lack of statistical power, inappropriate levels of anticoagulation, or lack of benefit of intravenous heparin. Large randomized studies of heparin (and of new antithrombotic regimens) are needed to establish the role of such therapy.

To compare the efficacy of 3-channel ambulatory electrocardiographic monitoring (Holter monitoring) with 2-channel Holter monitoring in the detection of transient myocardial ischemia (TMI), channels CM2, CM5, and modified II were studied. Sixty patients with documented coronary artery disease underwent 48-hour Holter monitoring during their normal daily life, followed by exercise stress testing in the laboratory monitored by means of radionuclide ventriculography and standard 12-lead electrocardiography. Analysis revealed that 3-channel Holter monitoring identified 24 patients with a total of 205 TMI episodes and a total ischemic burden of 371.00 mV-min. By itself, CM2 would have detected only 3 patients (13% of the TMI population), 6 TMI episodes (3% of the total TMI episodes), and a 2.4 mV-min ischemic burden (0.7% of the total ischemic burden). Modified II alone would have identified 17 patients (71% of the TMI population), 160 TMI episodes (78% of the total TMI episodes), and 307.24 mV-min of the ischemic burden (82% of the total ischemic burden). The combination of CM5/modified II identified 23 patients (96% of the TMI population), 201 TMI episodes (98% of the total TMI episodes), and 370.44 mV-min of the ischemic burden (98% of the total ischemic burden). These findings suggest that the electrode placement is more important than the absolute number of channels in the detection of TMI by Holter monitoring.

Forty-six patients with documented coronary artery disease were studied to examine the relation of cardiovascular reactivity to mental stress and cardiac vagal activity. Cardiac vagal activity was measured by means of frequency-domain analysis of heart rate variability with 48-hour out-of-hospital Holter monitoring. The amplitude of the high-frequency component (0.16 to 0.40 Hz) of heart rate variability is considered to be an index of cardiac vagal activity. Cardiovascular reactivity was measured in the laboratory during a 3-minute public speaking task. Results revealed that (1) the amplitude of the high-frequency component was significantly higher during sleep (24.6 +/- 11.3 ms) than during waking (18.2 +/- 8.0 ms) (p = 0.002); (2) compared to subjects with low diastolic blood pressure reactivity, those who displayed high diastolic blood pressure reactivity exhibited a significantly lower amplitude of the high-frequency component (19.2 +/- 6.9 vs 23.4 +/- 9.6 ms, p = 0.03). These results indicate that decreased cardiac vagal activity may contribute to the exaggerated diastolic blood pressure reactivity to mental stress in patients with coronary artery disease.

To determine the clinical features, course and outcome of patients with cardiac tamponade, 57 consecutive patients with new, large pericardial effusions were prospectively studied. Twenty-five patients (44%) developed cardiac tamponade with venous hypertension and a pulsus paradoxus greater than 10 mm Hg. Electrocardiography, radiographic studies and echocardiography did not differentiate patients with and without tamponade. All 57 patients underwent thorough diagnostic evaluation followed by subxiphoid pericardial biopsy and drainage. A diagnosis was obtained in 53 patients (93%). Collagen vascular disease was significantly more frequent in the 25 patients with than in the 32 without cardiac tamponade (24 vs 3%; p less than 0.05). The frequency of malignant and uremic effusions was equal in both groups, whereas radiation-induced effusions seldom produced tamponade. At 1-year follow-up, 3 patients (12%) with tamponade had recurrent effusions, and 1 needed reoperation. This was not significantly different from the 32 patients without tamponade. Twelve-month mortality was also similar in both groups (36 vs 44%). This prospective series disclosed several unexpected findings: (1) Cardiac tamponade occurred in almost 50% of patients with new large pericardial effusions; (2) both malignancy and collagen vascular disease occurred with equal frequency as etiologies, whereas radiation-induced tamponade was unusual; (3) thorough clinical evaluation resulted in few idiopathic etiologies; and (4) subxiphoid pericardiotomy was effective for both diagnosis and therapy of tamponade.

To document current management of uncomplicated acute myocardial infarction (AMI), a national survey of 1,065 physicians was performed. Items from previous surveys in 1970 and 1979 were included to permit analysis of time trends in management. Median hospital stay dropped from 21 days in 1970 to 9 days in 1987. Use of beta blockers and aspirin doubled between 1979 and 1987, while use of anticoagulation and sulfinpyrazone dropped 4- to 10-fold. In 1987, coronary angiography was used commonly, especially in younger patients or those with either a non-Q-wave AMI, intravenous thrombolytic therapy or a positive exercise test. These findings document the increasingly aggressive approach to the management of patients with uncomplicated AMI.

A national survey of 1,065 physicians was carried out to document current use of thrombolytic therapy for acute myocardial infarction (AMI). In early 1987, thrombolytic therapy was used by 66% of respondents. Among those who used thrombolytic therapy, 92% used streptokinase, 13% used tissue-type plasminogen activator and 3% used urokinase. Most (72%) used intravenous administration exclusively and only 5% used intracoronary administration exclusively. Despite widespread acceptance of thrombolytic therapy, most physicians gave it to less than 25% of their patients. Duration of symptoms was rated as the single most important factor affecting the decision to use thrombolytic therapy; 45% had a time limit of less than 4 hours and 85% had a time limit of less than 6 hours. Complications of AMI and electrocardiographic findings were factors also considered in the decision to give this therapy. A physician's adoption of thrombolytic therapy was significantly associated with several characteristics: specialty type, number of AMI patients treated, physician age and access to cardiac catheterization. In addition, physicians using thrombolytic therapy had a significantly different use of medications and laboratory tests for all patients with AMI. This survey documents rapid acceptance of thrombolytic therapy for AMI, particularly in patients with short duration of symptoms or evidence of high risk.