Dual antiplatelet therapy for more than 12 months after percutaneous coronary intervention: insights from the Guthrie PCI Registry.

OBJECTIVE: To assess the impact of dual antiplatelet (DAP) therapy of >12 months on long-term death and myocardial infarction (MI) after percutaneous coronary intervention (PCI). DESIGN, SETTING AND PATIENTS: Prospective, single-centre, observational study of 1859 consecutive patients who underwent successful PCI of a native coronary artery and survived event-free for at least 12 months. MAIN OUTCOME MEASURES: Combined end point of death or non-fatal MI determined by survival analysis and propensity-adjusted multivariable Cox regression. Similar analyses were performed in the two stent subsets: bare metal stents (n = 835), drug-eluting stents (n = 1024); and three high-risk subsets: diabetic patients (n = 486), patients presenting with MI (n = 713), and those with ACC/AHA type C lesions (n = 717). RESULTS: Baseline characteristics were as follows: mean (SD) age 64 (12) years, male 69%, diabetic 26%, presentation with MI 38%, mean (SD) ejection fraction 49 (12)%, mean (SD) vessel diameter 3.1 (0.5) mm. Duration of DAP was 27 (11) months in "DAP >12 months" and 4.1 (4.1) months in "DAP < or =12 months" (p<0.001). At a median follow-up of 3.4 years after PCI, "DAP >12 months" vs "DAP < or =12 months" had similar incidence of death or MI (9.4% vs 10.3%, log-rank p = 0.83). After multivariable adjustment, DAP therapy >12 months was not associated with lower incidence of death or MI than DAP therapy < or =12 months (adjusted HR = 1.01; 95% CI 0.74 to 1.37, p = 0.95). Analysis of each of the five predefined subsets showed similar results. CONCLUSIONS: In patients who undergo successful native coronary PCI and survive event-free for at least 12 months, continuation of dual antiplatelet therapy beyond 12 months does not confer long-term protection from death or MI.

Effect of combined aspirin and angiotensin-converting enzyme inhibitor therapy versus angiotensin-converting enzyme inhibitor therapy alone on readmission rates in heart failure.

An adverse interaction between aspirin and angiotensin-converting enzyme (ACE) inhibitors is suspected in patients with heart failure, but the effect of combined therapy with these agents on hospital readmission rates is unknown. Our study found that combining aspirin with ACE inhibitors is associated with higher early readmission rates than use of ACE inhibitors alone, particularly in patients with depressed ejection fraction and in those without coronary artery disease.

Simple clinical variables are markers of the propensity for readmission in patients hospitalized with heart failure.

In a consecutive cohort of patients hospitalized for decompensated heart failure, we found that chronic obstructive pulmonary disease and history of hospitalization for any cause in the preceding 6 months were the strongest correlates of early readmission. Based on these findings, we propose a simple risk stratification system to classify patients who are hospitalized for heart failure as low, medium, or high risk for early readmission.

Does left ventricular shape influence clinical outcome in heart failure?

BACKGROUND: Left ventricular (LV) shape tends to become spherical in patients with dilated cardiomyopathy of diverse etiology. Clinical and echocardiographic factors which affect the degree of LV spherical distortion and the impact of altered LV shape on prognosis have not been studied adequately. HYPOTHESIS: This study was undertaken to investigate the prognostic implications of altered LV shape on clinical outcome in dilated cardiomyopathy. METHODS: In 112 patients with depressed LV ejection fraction (19 +/- 9%) and symptomatic heart failure, and in 10 age- and gender-matched normal controls, we performed 2-dimensional echocardiography to assess LV shape using the eccentricity index. Eccentricity index was defined as the ratio of the LV long axis to the LV transverse diameter, measured at end systole and end diastole in the apical four-chamber view. We sought univariate and multivariate clinical and echocardiographic correlates of LV shape. Further, we sought correlations between eccentricity index and clinical outcomes (death and composite outcome of death or emergent heart transplant). RESULTS: Compared with controls, patients with cardiomyopathy had significantly lower systolic (2.04 vs. 1.56; p = 0.001) and diastolic (1.75 vs. 1.53; p = 0.003) eccentricity index, implying a more spherical LV shape. Of all clinical and echocardiographic variables tested, mitral regurgitation, right ventricular dysfunction, and increased LV mass were independently associated with spherical LV shape. At a follow-up period of 17 +/- 12 months, no correlation was found between eccentricity index and the occurrence of death or the combined endpoint of death or emergent heart transplant, in univariate or multivariate analysis. CONCLUSIONS: In patients with dilated cardiomyopathy, the degree of spherical distortion of the LV does not correlate with prognosis.

Does gender bias exist in the medical management of heart failure?

INTRODUCTION: The purpose of this study was to ascertain the presence of gender bias in the medical management of heart failure, and to assess its association with the specialty of the caregiver physician. METHODS: In 309 patients with documented left ventricular systolic dysfunction (ejection fraction <45%) and at least one hospitalization for heart failure, we assessed the frequency of use of effective medical therapy for heart failure among male (n=187) and female (n=122) patients at the time of hospital discharge. We constructed multivariate models relating patient gender and caregiver specialty to utilization of each class of medications (angiotensin-converting enzyme inhibitors, effective vasodilator therapy (i.e., angiotensin-converting enzyme inhibitors or hydralazine-nitrate therapy), diuretics, digoxin), and combination therapy (i.e., vasodilator plus diuretic plus digoxin). RESULTS: In crude analyses, we did not find any difference in utilization of medications between male and female patients. Multivariate analyses involving adjustment for age, race, coronary artery disease, ejection fraction, and other relevant variables, revealed higher utilization of combination therapy by cardiologists in male versus female patients (adjusted odds ratios=2.07; 95%CI=1.09-3.95), and higher utilization of digoxin therapy by non-cardiologists in female versus male patients (adjusted odds ratio=5.5; 95%CI=1.4-22.2). No gender or caregiver specialty differences were seen in models relating to the other classes of medications. CONCLUSIONS: Our findings suggest the presence of gender bias in the medical management of heart failure, and identify an interesting interaction between caregiver specialty and gender bias.

New paradigms in preventive cardiology: unconventional coronary risk factors.

The 1996 Bethesda Conference acknowledged the following conditions as possible new cardiac risk factors: left ventricular hypertrophy, homocysteine, lipoprotein(a), hypertriglyceridemia, oxidative stress, and fibrinogen. Left ventricular hypertrophy is an independent risk factor for vascular disease, the improvement or progression of which influences subsequent cardiovascular complications. Clinical trials are currently underway to assess potential benefit from lowering homocysteine levels. The role of lipoprotein(a) excess in vascular disease is controversial; its atherogenic potential seems to be neutralized by effective lowering of LDL-cholesterol. Increasing evidence supports the independent role of hypertriglyceridemia in cardiovascular disease and possible clinical benefit from lowering triglyceride levels. Among antioxidant micronutrients, supplementation with vitamin E has been shown to be beneficial in some but not all primary and secondary prevention studies, but data to support use of other antioxidants are much weaker. Preliminary evidence suggests that the reduction of fibrinogen levels in patients with high baseline levels and coronary disease may be beneficial.Despite the potential relation between new risk factors and cardiovascular disease, routine clinical application of these conditions as cardiovascular risk factors would be premature. We first need evidence that these conditions extend prognostic ability beyond conventional risk factors and that modification of these conditions can decrease the risk of cardiovascular events.

Potential new cardiovascular risk factors: left ventricular hypertrophy, homocysteine, lipoprotein(a), triglycerides, oxidative stress, and fibrinogen.

The 1996 Bethesda Conference acknowledged left ventricular hypertrophy, hyperhomocysteinemia, lipoprotein(a) excess, hypertriglyceridemia, oxidative stress, and hyperfibrinogenemia as possible new cardiac risk factors. This review summarizes the current literature that supports these conditions as cardiac risk factors. Left ventricular hypertrophy is an independent risk factor for vascular disease. Improvement or progression of left ventricular hypertrophy influences subsequent cardiovascular complications. Clinical trials are under way to assess the potential benefit of decreasing homocysteine levels. The role of lipoprotein(a) excess in vascular disease is controversial. The atherogenic potential of lipoprotein(a) seems to be neutralized by effective reduction of low-density lipoprotein cholesterol levels. Increasing evidence supports an independent role of hypertriglyceridemia in cardiovascular disease and a possible clinical benefit from decreasing triglyceride levels. Among antioxidant micronutrients, supplementation with vitamin E has been shown to be beneficial in primary and secondary prevention studies. Data supporting the use of other antioxidants are much weaker. Preliminary evidence suggests that reducing fibrinogen levels in patients with high baseline levels and coronary disease may be beneficial. Despite the potential relation between new risk factors and cardiovascular disease, routine clinical application of these conditions as cardiovascular risk factors would be premature. Evidence is needed that these conditions extend prognostic ability beyond conventional risk factors and that modification of these conditions can reduce the risk for cardiovascular events.

The independent effects of left ventricular ejection fraction on short-term outcomes and resource utilization following hospitalization for heart failure.

BACKGROUND: While depressed left ventricular ejection fraction is clearly associated with poor long-term outcome in heart failure (HF), the effect of ejection fraction on short-term outcomes and resource utilization following hospitalization for HF remains unclear. HYPOTHESIS: We evaluated the independent effect of depressed ejection fraction (< or = 40%) on short-term outcomes and resource utilization following hospitalization for HF. METHODS: The study population included 443 consecutive patients hospitalized for DRG 127 (HF and shock) with known ejection fraction. For each patient, we assessed the hospitalization cost (1995 US$), length of stay, in-hospital mortality, 30-day mortality, and 30-day readmission rates. RESULTS: Despite similar disease severity at admission, patients with ejection fraction < or = 40% (Group 1) had longer length of stay (4.0 vs. 3.7 days; p = 0.03), a tendency toward higher hospitalization cost ($3,054 vs. $2,770; p = 0.08), more readmissions for any cause (0.4 vs. 0.3; p = 0.05) and for HF (0.2 vs. 0.1; p = 0.01), but similar in-hospital (2.5 vs. 2.6%) and 30-day mortality (4.0 vs. 4.6%) compared with patients with ejection fraction > 40% (Group 2). In multivariate analyses, Group 1 patients were more likely to have higher than median hospitalization cost [odds ratio (OR) = 1.98; 95% confidence intervals (CI) = 1.02-3.91] and longer than median hospital stay (OR = 1.68; CI = 1.08-3.91); they were also more likely to be readmitted for any cause (OR = 2.07; CI = 1.15-3.78) or for HF (OR = 5.71; CI = 1.64-21.94), and they tended to have a higher 30-day incidence of death or readmission (OR = 1.65; CI = 0.96-2.84). CONCLUSIONS: Depressed left ventricular ejection fraction is associated with higher resource utilization and readmission rates following hospitalization for HF. Greater focus on patients with depressed ejection fraction may increase cost savings from HF disease management programs.

The prognostic implications of outpatient diuretic dose in heart failure.

In 111 patients with left ventricular ejection fraction < or =30% who required hospitalization for heart failure, we examined the association between outpatient dose of diuretic agents and all-cause mortality. In comparison to patients who were not on treatment with diuretics prior to hospitalization, patients being treated with 'low' doses of diuretics (<80 mg/day of furosemide) and those being treated with 'high' doses of diuretics (> or =80 mg/day of furosemide) were more likely to die during follow-up after adjustment for other clinical parameters (adjusted relative risks, RR, 3.1 and 4.6).

Acute coronary occlusion and in-stent thrombosis in a patient with essential thrombocythemia.

We describe a case of essential thrombocythemia in a 34-year-old male who presented with acute anterior wall myocardial infarction and a platelet count of 2,100,000/mm3. Primary percutaneous coronary angioplasty and stenting were performed. Postangioplasty course was complicated by stent thrombosis requiring repeat coronary angioplasty and persistent femoral arterial bleeding that was treated with surgical exploration and repair. The patient was subsequently treated with platelet pheresis, acetylsalicylic acid, ticlopidine, hydroxyurea, and anagrelide without further complications.

Effects of caregiver specialty on cost and clinical outcomes following hospitalization for heart failure.

In 614 consecutive hospitalizations with the primary discharge diagnosis of diagnosis-related group (DRG) 127 (heart failure and shock), we sought to assess the effect of caregiver specialty (generalist, n = 217; cardiologist, n = 397) on hospital costs, length of stay, and in-hospital mortality. Patients treated by cardiologists were younger (68 vs 71 years) and less likely to have hypertension (52% vs 61%), but were more likely to be men (61% vs 44%), require an intensive care stay (13% vs 5%), have coronary artery disease (49% vs 23%), have a left ventricular ejection fraction <40% (74% vs 49%), and have lower systolic (132 vs 146 mm Hg) and diastolic (76 vs 81 mm Hg) blood pressures on admission. Predictors of acute disease severity were similarly distributed between the 2 groups. No difference was found between patients treated by cardiologists versus those treated by generalists with respect to crude or adjusted hospital cost, length of stay, and in-hospital mortality. However, in subsets of patients who required intensive care during hospitalization (n = 64), as well as those who did not (n = 550), care by cardiologists was associated with a lower adjusted hospital cost. Any potential cost savings that could have accrued from care by cardiologists was, however, negated by the higher proportion of patients treated by cardiologists who required intensive care during hospitalization. We conclude that when differences in clinical variables are adjusted, care by cardiologists versus generalists is associated with similar or lower hospital cost for patients with DRG 127. Our findings challenge the notion that in-patient care provided by specialists is more expensive than that provided by generalists.

Home inotropic therapy in advanced heart failure: cost analysis and clinical outcomes.

STUDY OBJECTIVES: This study was conducted to assess cost savings and clinical outcomes associated with the use of home i.v. inotropic therapy in patients with advanced (New York Heart Association [NYHA] class IV) heart failure. DESIGN: Retrospective analysis. SETTING: Tertiary care referral center. PATIENTS AND INTERVENTIONS: Twenty-four patients (13 men, 11 women; age, 61+/-12 years) with left ventricular ejection fraction <30% and heart failure refractory to oral agents required home i.v. inotropic therapy for at least 4 consecutive weeks between May 1994 and April 1996. Inotropic agents used included dobutamine (n=20; dose, 5.0+/-2.2 microg/kg/min) or milrinone (n=7; dose, 0.53+/-0.05 microg/kg/min). MEASUREMENTS AND RESULTS: Cost of care and clinical outcomes (hospital admissions, length of hospital stay, NYHA functional class) were compared during the period of inotropic therapy (study period) and the immediate preceding period of equal duration (control period). In comparison to the control period, the study period (3.9+/-2.7 months) was associated with a 16% reduction in cost, amounting to a calculated savings of $5,700 per patient or $1,465 per patient per month. Concomitantly, a decrease in the number of hospital admissions from 2.7+/-2.6 to 1.3+/-1.3 (p=0.056) and length of hospital stay from 20.9+/-12.7 to 5.5+/-5.4 days (p=0.0004) was observed with improvement in NYHA functional class from 4.0+/-0.0 to 2.7+/-0.9 (p<0.0001). Eight patients (38%) died after 2.8+/-1.7 months of home i.v. inotropic therapy. CONCLUSIONS: Home i.v. inotropic therapy reduces hospital admissions, length of stay, and cost of care and improves functional class in patients with advanced (NYHA class IV) heart failure.

Clinical variables affecting recovery of left atrial mechanical function after cardioversion from atrial fibrillation.

OBJECTIVES: We sought to evaluate the effect of clinical factors on recovery of atrial function after cardioversion for atrial fibrillation. BACKGROUND: Lack of effective mechanical atrial function (EMAF) after cardioversion of atrial fibrillation predisposes to thromboembolic complications and delays improvement in functional capacity. METHODS: Fifty-two patients underwent cardioversion (group I, electrical cardioversion, n = 40; group II, pharmacologic or spontaneous cardioversion, n = 12) for atrial fibrillation. Serial transmitral inflow Doppler variables were recorded after cardioversion until EMAF (atrial filling velocity > 0.50 m/s) was seen. Clinical variables (age, duration of atrial fibrillation, left ventricular ejection fraction, left atrial diameter, underlying cardiovascular disease, antiarrhythmic drug therapy and mode of cardioversion) were tested for an association with the outcomes of recovery of atrial function by day 3 and day 7. RESULTS: Effective mechanical atrial function recovered in 68% of patients by day 3 and in 76% by day 7 after cardioversion. The mode of cardioversion was significantly associated with recovery of atrial function by day 3 in bivariate and multivariate analyses (odds ratio 0.12, 95% confidence interval 0.01 to 1.0, for electrical cardioversion). None of the variables had an association with recovery of atrial function by day 7. Group I patients took a longer time to recover atrial function than group II patients (p = 0.012). In addition, group I patients had a significantly lower peak atrial filling velocity (mean [+/-SD] 0.39 +/- 0.19 m/s vs. 0.56 +/- 0.16 m/s) and a higher early filling to atrial filling velocity ratio (2.5 +/- 1.2 vs. 1.5 +/- 0.5) after cardioversion. CONCLUSIONS: A high proportion of patients recover EMAF within 1 week after cardioversion. Patients who undergo electrical cardioversion display a greater degree and a longer duration of mechanical atrial dysfunction than those who convert pharmacologically or spontaneously.

Effects of amiodarone on thyroid function.

PURPOSE: To review the literature on the effects of amiodarone on thyroid physiology and management of amiodarone-induced thyroid disease. DATA SOURCES: English-language articles identified through a MEDLINE search (for 1975 to 1995, using the terms amiodarone and thyroid) and selected cross-referenced articles. STUDY SELECTION: Articles on the effects of amiodarone on thyroid physiology and function tests and occurrence, recognition, and management of amiodarone-induced thyroid disease. DATA EXTRACTION: Data were manually extracted from selected studies and reports; emphasis was placed on information relevant to the practicing clinician. DATA SYNTHESIS: Amiodarone can have many effects on thyroid function test results, even in the absence of hyperthyroidism or hypothyroidism. It may cause an increase in serum levels of thyroxine, reverse triiodothyronine, and thyroid-stimulating hormone and a decrease in serum triiodothyronine levels. Thyrotoxicosis occurs in some patients and is related to several pathogenetic mechanisms. It often present dramatically with obvious clinical manifestations and further changes in thyroid function test results. Medical options include therapy with thionamides, perchlorate, and prednisone. Radioactive iodine is of little use. Thyroidectomy is effective and is the only measure that consistently allows continued use of amiodarone. Unlike thyrotoxicosis, hypothyroidism is related to a persistent Wolff-Chaikoff effect and often has a vague presentation. The goal of treatment of amiodarone-induced hypothyroidism is to bring serum thyroxine levels to the upper end of the normal range, as often seen in euthyroid patients who are receiving amiodarone. CONCLUSIONS: Thyroid dysfunction commonly occurs with amiodarone therapy. It may be difficult to recognize the dysfunction because of the many changes in thyroid function test results that occur in euthyroid patients who are receiving amiodarone. Effective strategies exist for the management of hyperthyroidism and hypothyroidism; these should be tailored to the needs of the individual patient.

Amiodarone induced hyperthyroidism: a case series and brief review of literature.

To delineate the incidence, clinical features, diagnosis, and treatment options for amiodarone induced hyperthyroidism (AIH), we reviewed the medical records of ten patients with AIH. Eight of these 10 patients were detected on initial review of the records of 200 patients in treatment with amiodarone, and the other 2 following notification by their endocrinologists. AIH occurred in 4.2% of patients being treated with amiodarone. At the time of diagnosis of AIH, the mean (SD) values for age, duration of treatment with amiodarone, and dose of amiodarone were 62.9 (8.96) years, 38.3 (20) months, and 366.7 (122) mg/day, respectively. The most common clinical features were weight loss and goiter (each seen in 90% of patients). Serum thyroxine (T4), triiodothyronine, and free thyroxine index (FTI) showed an increase of 84%, 47%, and 110%, while thyroid stimulating hormone (TSH) and resin T4 uptake decreased 96% and 14%, respectively, from previous values. The most consistent laboratory findings, seen in all patients, were subnormal TSH and abnormally high FTI. One patient required no treatment; another underwent prompt total thyroidectomy. The other eight were treated medically; two of them underwent total thyroidectomy later, for medical failure or adverse effects. Amiodarone was continued in four patients. The most commonly used antithyroid medication was propylthiouracil. AIH presents in the early or late phases of treatment with amiodarone with typical clinical features of a hyperthyroid state, fall in TSH, and increase in FTI. Antithyroid medications are reasonably effective in the management of AIH.

Ischemia and atherosclerotic coronary artery disease in patients with hypertrophic cardiomyopathy: a review of incidence, pathophysiological mechanisms, clinical implications and management strategies.

Ischemia is suspected to occur frequently in patients with HCM and may result from various mechanisms, for example decreased coronary flow reserve, disease of small intramuscular arteries, "inadequate' size of coronary arteries relative to hypertrophied myocardium, diminution of coronary flow during systole, compression of septal perforator arteries during systole, coronary artery spasm, and co-existent atherosclerotic CAD, which can be present in up to a quarter of HCM patients above 45 years of age. The diagnosis of CAD in patients with HCM is difficult to make on clinical grounds, secondary to the high frequency of angina in patients with HCM without CAD. Pharmacological stress echocardiography is promising but needs to be further studied; stress thallium imaging is beset with frequent false positive results. At this time, coronary angiography remains the only reliable test for the definitive diagnosis of co-existent CAD in HCM. Beta-blockers and verapamil may help in relieving symptoms and silent ischemia in patients with HCM; in those with coexistent CAD and resistant symptoms, CABG alone or in combination with left ventricular myectomy or mitral valve replacement has been recommended.

Thrombotic tendencies and correlation with clinical status in patients infected with HIV.

Previous publications have described thrombotic events with unclear causes in individuals infected with the human immunodeficiency virus (HIV). We stratified the cases of 52 individuals infected with HIV by degree of immunosuppression and the presence of complicating illnesses. Plasma from these individuals was screened for abnormalities that might predispose to thromboses. We found statistically significant differences between patients with CD4 counts < 200/mm3 and those whose CD4 counts were > 400/mm3 in the following: d-dimers, functional protein C, antigenic protein C, total protein S antigen, free protein S antigen, C4b-binding protein (C4b-BP), and von Willebrand antigen (vWD). Free protein S correlated inversely with C4b-BP; vWD directly with total protein S; and protein C inversely with d-dimers. D-dimers were significantly elevated only in immunosuppressed patients with complicating neoplastic/inflammatory disease. We propose that low-grade disseminated intravascular coagulopathy in severely immunosuppressed individuals with HIV and infectious, inflammatory, or neoplastic complications is responsible for depressed protein C, which, together with elevations in total protein S and vWD (markers of endothelial injury), indicates a thrombotic predisposition.

Portal venous pressure and the serum-ascites albumin concentration gradient.

CLINICAL ISSUE: Other investigators have found the serum-ascites albumin concentration gradient to be 1.1 g/dL or greater in the presence of portal hypertension and less than that in its absence. OBJECTIVE: To determine if any correlation exists between the serum-ascites albumin concentration gradient (which reflects the net serum oncotic pressure) and the portal venous pressure. METHODS: The study group comprised 15 patients who had alcoholic cirrhosis. The portal venous pressure was calculated as the difference between the measured hepatic venous wedge and inferior vena cava pressures and was expressed as the hepatic venous pressure gradient. SUMMARY: All patients had portal hypertension; the mean hepatic venous pressure gradient was 14.81 +/- 6.91 (SD) mm Hg. Fourteen of the 15 patients had a serum-ascites albumin concentration gradient of at least 1.1 g/dL; the mean value was 2.168 +/- .709 g/dL. No correlation was found between these variables (r = .0459, P > .05). CONCLUSIONS: Although the serum-ascites albumin concentration gradient is a sensitive indicator of portal hypertension in patients with alcoholic cirrhosis, it does not reflect the portal venous pressure.