Heparin-induced thrombocytopenia: analysis of risk factors in medical inpatients.

Heparin-induced thrombocytopenia (HIT) is an unpredictable reaction to heparin characterized by thrombocytopenia and increased risk of life-threatening venous and/or arterial thrombosis. Data are lacking regarding additional risk factors that may be associated with the development of HIT. This study aimed to identify the risk factors that may be associated with HIT in medical inpatients receiving heparin. Twenty five thousand six hundred and fifty-three patients admitted to the medicine service who received heparin product were reviewed retrospectively. The diagnosis of HIT was confirmed if the platelet count dropped >50% from baseline and there was a positive laboratory HIT assay. Fifty-five cases of in-hospital HIT were observed. Multivariate analysis identified the administration of full anticoagulation dose with unfractionated heparin or exposure to heparin products for more than 5 d with an increased risk of HIT. Moreover, patients who were on haemodialysis, carried a diagnosis of autoimmune disease, gout or heart failure were also at increased risk. The results suggest that when using heparin products in these patient cohorts, increased surveillance for HIT is necessary.

Fatty acid imaging of the heart.

Imaging metabolic processes in the human heart yields valuable insights into the mechanisms contributing to myocardial pathology and allows assessment of the efficacy of therapies designed to treat cardiac disease. Recent advances in fatty acid (FA) imaging using positron emission tomography (PET) include the development of a method to assess endogenous triglyceride metabolism and the design of new fluorine-18 labeled tracers. Studies of patients with diabetes have shown that the heart is resistant to insulin-mediated glucose uptake and that metabolism of nonesterified FA is upregulated. Cardiac PET imaging has also recently shown the increase in myocardial FA uptake seen in obese patients can be reversed with weight loss. And a pilot study of patients with chronic kidney disease demonstrated that PET imaging can reveal myocardial metabolic alterations that parallel the decline in estimated glomerular filtration rate. Recent advances in FA imaging using single photon emission computed tomography (SPECT) have been accomplished with the tracer ß-methyl-p-[(123)I]-iodophenyl-pentadecanoic acid (BMIPP). Two meta-analyses showed this imaging technique has a diagnostic accuracy for the detection of obstructive coronary artery disease that compares favorably with SPECT myocardial perfusion imaging and that BMIPP imaging yields excellent prognostic data in patients across the spectrum of coronary artery disease. A recent multicenter study of patients presenting with acute coronary syndromes found BMIPP SPECT imaging has greater diagnostic sensitivity than, and enhances the negative predictive value of, clinical assessment alone. Because of their exquisite sensitivity, nuclear imaging techniques facilitate the study of physiologic processes that are the key to our understanding of cardiac metabolism in health and disease.

Prognostic value of myocardial metabolic imaging with BMIPP in the spectrum of coronary artery disease: a systematic review.

BACKGROUND: We conducted a systematic review to summarize the current literature on the prognostic value of BMIPP imaging, fatty-acid metabolic imaging, for the prediction of cardiovascular events in coronary artery disease. METHODS AND RESULTS: Electronic databases (including Japanese medical literature search engines) were searched by a Japanese investigator using a predefined search strategy. Eleven studies, all conducted in Japan, were included in the meta-analysis. In three studies involving 541 patients with suspected acute coronary syndrome who were excluded for acute myocardial infarction (AMI), an abnormal finding on BMIPP imaging was significantly associated with future hard events (cardiac death or non-fatal myocardial infarction). The negative predictive value of BMIPP imaging for future hard events was 98.9% (96.8-99.7%) over 3.5 years. In six studies involving 542 patients with AMI, a larger defect on BMIPP imaging was significantly associated with future hard events. The prognostic value of perfusion-metabolism mismatch compared with myocardial perfusion imaging was dependent upon the relative timing of BMIPP imaging, revascularization, and myocardial perfusion damage. CONCLUSIONS: BMIPP imaging is useful for the risk stratification of patients with coronary artery disease, particularly patients with acute chest pain.

Quantity of viable myocardium required to improve survival with revascularization in patients with ischemic cardiomyopathy: A meta-analysis.

BACKGROUND: This meta-analysis was conducted to determine optimal cutoff values for the assessment of viability using various imaging techniques for which revascularization would offer a survival benefit in patients with ischemic cardiomyopathy (ICM). METHODS AND RESULTS: We searched five electronic databases to identify relevant studies through December 2008. Relative risks of cardiac death, both in patients with and without viability, were calculated in each study. In order to estimate the optimal threshold for the presence of viability, we assumed a linear relationship between the amount of viable myocardium and survival benefit of revascularization. Twenty-nine studies (4,167 patients) met the inclusion criteria. The optimal threshold for the presence of viability was estimated to be 25.8% (95% CI: 16.6-35.0%) by positron emission tomography using 18F-fluorodeoxyglucose-perfusion mismatch, 35.9% (95% CI: 31.6-40.3%) by stress echocardiography using contractile reserve or ischemic responses, and 38.7% (95% CI: 27.7-49.7%) by single photon emission computed tomography using thallium-201 or technetium-99m MIBI myocardial perfusion. CONCLUSIONS: The calculated amount of viable myocardium determined to lead to improved survival was different among imaging techniques. Thus, separate cutoff values for imaging modalities may be helpful in determining which patients with ICM benefit from revascularization.

Diagnostic accuracy of beta-methyl-p-[123I]-iodophenyl-pentadecanoic acid (BMIPP) imaging: a meta-analysis.

BACKGROUND: beta-Methyl-p-[(123)I]-iodophenyl-pentadecanoic acid (BMIPP) imaging has been used extensively to detect coronary artery disease (CAD), primarily in Japan. However, the reported sensitivity and specificity vary considerably from study to study. This meta-analysis was conducted to summarize the evidence for the diagnostic accuracy of resting BMIPP imaging in the detection of CAD. METHODS AND RESULTS: A MEDLINE search of the literature published through the end of 2006 was performed. Seven studies (528 patients) met the inclusion criteria. Using random-effects models, the overall sensitivity and specificity to detect CAD were 78% (95% confidence interval, 73% to 81%) and 84% (95% confidence interval, 77% to 89%), respectively. A significant threshold effect was identified among studies, which was expected given the between-study variability in study methodology. A summary receiver-operating characteristic curve yielded an asymmetric curve with an area under the curve of 0.91 (SE, 0.020), indicating excellent diagnostic performance. CONCLUSIONS: Imaging with BMIPP at rest exhibits a moderate sensitivity and high specificity to detect CAD in patients with a high prevalence of CAD. Thus, this tracer may be of great value for patients with acute chest pain and those with relative contraindications to exercise or pharmacologic stress myocardial perfusion imaging (MPI).

Differences in diagnostic evaluation and clinical outcomes in the care of patients with chest pain based on admitting service: the benefits of a dedicated chest pain unit.

BACKGROUND: Chest pain is one of the most common complaints of patients presenting at emergency departments. However, the most appropriate diagnostic evaluation for patients with chest pain but without acute coronary syndrome remains controversial, and differs greatly among institutions and physicians. At our institution, patients with chest pain can be admitted to an internist-run hospitalist service, a private attending service, or a cardiologist-run Chest Pain Unit. The goal of the present study was to compare the management and outcomes of patients admitted with chest pain based on admitting service. METHODS: The charts of 750 patients (250 consecutive patients per service) with a discharge diagnosis of chest pain were studied retrospectively. RESULTS: Patients admitted to the Chest Pain Unit were younger and had a lower prevalence of known coronary artery disease, hypertension, or diabetes, but a similar prevalence of other risk factors compared with the other groups. Sixty percent of the patients in the Chest Pain Unit underwent stress myocardial perfusion imaging as their primary diagnostic modality (vs 22% and 12% of patients in the hospitalist and private services, respectively; P < .001). In contrast, 35% of the patients admitted to the hospitalist service underwent rest echocardiography (vs 8% and 17% of patients in the Chest Pain Unit and private services, respectively; P < .001). Finally, 47% of the patients in the private service underwent coronary angiography as their primary diagnostic modality (vs 6% and 10% of patients in the Chest Pain Unit and hospitalist services, respectively; P < .001). The length of stay was shortest for patients in the Chest Pain Unit (1.4 +/- 1.2 days vs 3.9 +/- 3.4 days and 3.5 +/- 3.6 days in the hospitalist and private services, respectively; P < .001), even when corrected for patient age and number of risk factors. Readmission within 6 months was lowest for patients in the Chest Pain Unit (4.4% vs 17.6% and 15.2% in the hospitalist and private services, respectively; P < .001). CONCLUSIONS: The results of this study demonstrate that a highly protocolized chest pain unit, using myocardial perfusion imaging as primary diagnostic modality, results in a decreased length of stay and readmission rate.

Superiority of exercise myocardial perfusion imaging compared with the exercise ECG in the diagnosis of coronary artery disease.

BACKGROUND: Wide variations in the sensitivity and specificity of the exercise ECG for the diagnosis of coronary artery disease (CAD) have been reported. The aim of this study was to reexamine the sensitivity and specificity of the stress ECG and stress myocardial perfusion imaging (MPI) relative to cardiac catheterization in an era of aggressive screening. METHODS AND RESULTS: We evaluated 218 patients [mean age: 62+/-13 (SD) years; 69% males] with symptoms of chest pain or dyspnea, normal resting ECGs, and no earlier myocardial infarction. All patients exercised to age-corrected and sex-corrected Bruce protocol times and achieved >or=85% of predicted maximum heart rate. Coronary angiography was performed within 3 months of stress testing. Sixty-six percent of patients had significant CAD by angiography. The overall sensitivity of the exercise ECG (36%) was significantly lower than that of exercise MPI (81%) (P<0.001). In addition, the specificity of the exercise ECG was higher in men than in women (94% men, 74% women; P<0.01), whereas there were no significant differences in sensitivity or specificity (79%) of MPI between men and women. In patients with multivessel CAD or proximal left anterior descending stenosis >or=70%, the sensitivity of the exercise ECG was higher (58%), but still less than MPI (88%) (P<0.01). CONCLUSION: MPI is vastly superior to the stress ECG for the diagnosis of CAD, especially in patients with single-vessel CAD. Older literature reporting higher sensitivity for the stress ECG was likely biased by patients with more severe CAD and must be reexamined in the era of earlier diagnosis and intervention.

Metabolic imaging with beta-methyl-p-[(123)I]-iodophenyl-pentadecanoic acid identifies ischemic memory after demand ischemia.

BACKGROUND: After myocardial ischemia, prolonged suppression of fatty acid metabolism may persist despite restoration of blood flow, which is called metabolic stunning. We hypothesized that a branched-chain fatty acid, beta-methyl-p-[(123)I]-iodophenyl-pentadecanoic acid (BMIPP), might identify the presence of myocardial ischemia late after demand ischemia at rest up to 30 hours later. METHODS AND RESULTS: In 32 patients with exercise-induced ischemia on thallium SPECT, BMIPP was injected at rest within 30 hours of ischemia. SPECT images were acquired beginning 10 minutes after injection (early) and again 30 minutes after injection (delayed). Thallium and BMIPP SPECT data were read separately by 3 observers blinded to other imaging and clinical data. Agreement between BMIPP and thallium data for the presence of an abnormality on the patient level was 91% (95% CI, 75 to 98) for the early BMIPP data and 94% (95% CI, 79 to 99) for the delayed BMIPP data. Agreement between delayed BMIPP and thallium was 95% among 21 patients studied on the same day, a mean of 6.2+/-1.4 hours after exercise-induced ischemia, and 91% among the 11 patients studied on the next calendar day, a mean of 24.9+/-2.6 hours after ischemia (P=NS). The magnitude of resting BMIPP metabolic defect by semiquantitative visual analysis was correlated to the magnitude of exercise-induced thallium perfusion defect (r=0.6, P<0.001 for early BMIPP; r=0.5, P=0.005 for delayed BMIPP). CONCLUSIONS: Metabolic imaging with BMIPP identifies patients with recent exercise-induced myocardial ischemia. These findings support the concept that BMIPP imaging can successfully demonstrate the metabolic imprint of a stress-induced ischemic episode, also known as ischemic memory.

Effects of tadalafil on myocardial blood flow in patients with coronary artery disease.

OBJECTIVE: Erectile dysfunction and coronary artery disease share similar risk factors. Although phosphodiesterase-5 inhibitors used to treat erectile dysfunction do not adversely affect hemodynamic parameters in patients with coronary artery disease, their effects on myocardial blood flow are unknown. METHODS: In a randomized, double-blind, crossover study we examined the effects of tadalafil, 20 mg, compared with placebo on myocardial blood flow in patients with stable coronary artery disease (n=7, 52-73 years old). After tadalafil or placebo, myocardial blood flow was measured with positron emission tomography (nine-segment model) at rest, during maximal coronary hyperemia with adenosine, and during increased myocardial work with dobutamine. Abnormal flow was defined as myocardial blood flow <75% of maximum perfusion during adenosine plus placebo (46 normal/17 abnormal segments dentified). RESULTS: Compared with placebo, tadalafil had no significant effect on global myocardial blood flow at rest, during adenosine infusion, or during dobutamine infusion. Similarly, in normal and abnormal segments, tadalafil versus placebo had no significant effect on resting myocardial blood flow or on adenosine-induced increases in myocardial blood flow. In normal segments, myocardial blood flow with dobutamine plus tadalafil was greater than that with dobutamine plus placebo (1.79+/-0.56 versus 1.56+/-0.37 ml/g per min, P<0.01), and in abnormal segments, there was a trend for tadalafil compared with placebo to increase myocardial blood flow during dobutamine infusion (1.46+/-0.44 versus 1.36+/-0.36 ml/g per min, P=0.7). CONCLUSIONS: Tadalafil had no significant effect on global myocardial blood flow at rest, during adenosine infusion, or during dobutamine infusion. Compared with placebo, tadalafil significantly augmented myocardial blood flow during increased workload in normal regions, with a trend toward improving myocardial blood flow in poorly perfused regions.

Cardiac risk factors, medicine usage, and hospital course in immigrants from the former Soviet Union.

Immigrants from the former Soviet Union have a higher prevalence of cardiac risk factors and more problems obtaining health care in the United States than American-born Caucasians. This study compared differences between patients of these two populations admitted for diagnosis of chest pain or shortness of breath. Immigrants from the former Soviet Union (who had been in the U.S. for an average of 20 years) had more cardiac risk factors than American-born Caucasians including more hypertension (81% vs. 50%, p=.002), positive family history (53% vs. 30%, p=.030), more previous heart attacks (45% vs. 20%, p=.012), more prior cardiac catheterizations (51% vs. 18%, p<.001) and coronary revascularization procedures (51% vs. 27%, p=.022), and higher systolic blood pressure (138+/-13 vs. 129+/-23 mmHg, p=.019) upon presentation to the hospital. Fifty-five percent of immigrant patients used foreign medications. Thus, there are major differences between immigrants from the former Soviet Union who are admitted to the cardiac units of an urban New York hospital and American-born Caucasians. Knowledge of these differences is important for caregivers.

Effectiveness and outcomes of a nurse practitioner-run chest pain evaluation unit.

BACKGROUND: Every year, more than 5 million patients seek medical care for chest pain. OBJECTIVE: The goal of this study was to evaluate test utilization and outcomes of a nurse practitioner (NP)-based chest pain unit and compare results to data previously reported from our institution. DESIGN, SETTING, AND PARTICIPANTS: The records from 814 consecutive patients with chest pain admitted to the NP-run unit were compared to the outcomes of 250 patients admitted to a separate hospitalist-run unit at a New York City hospital. RESULTS: Forty-four percent of patients in the NP unit underwent stress myocardial perfusion imaging (MPI) as the primary diagnostic test (compared to 22% in the hospitalist unit, p < .0001). The average length of stay was shorter for patients in the NP unit (2.7 ± 3.6 days compared to 3.9 ± 3.4 days, p < .0001). Additionally, the 90-day readmission rate was less for patients in the NP unit (2.7% vs. 3.9%, p < .0006). CONCLUSIONS: An NP-run chest pain unit resulted in decreased length of stay and reduced readmission rates compared to a hospitalist-based unit.

The effect of estrogen compared to estrogen plus progesterone on the exercise electrocardiogram.

OBJECTIVES: The objective of this study was to evaluate the effect of estrogen compared to estrogen plus progesterone on the stress electrocardiogram (ECG) in relationship to stress-gated myocardial perfusion imaging (MPI) in postmenopausal women. BACKGROUND: It is generally recognized that estrogen may cause false positive ST depressions on the stress ECG. The effects of estrogen plus progesterone are not known. This study was performed to define the effects of these agents on the stress ECG correlated with results from MPI. METHODS: We evaluated 140 postmenopausal women-31 not taking any hormone replacement therapy (HRT); 75 taking estrogen alone; and 34 taking estrogen plus progesterone. Women with a history of coronary artery disease (CAD), cardiomyopathy, or an abnormal resting ECG were excluded. All women underwent a symptom-limited treadmill test and MPI. RESULTS: The overall sensitivity and specificity of the stress ECG compared to MPI in women not taking HRT was 54% and 78%, respectively. In women taking estrogen or estrogen plus progesterone, the sensitivity was unchanged. The power to detect clinically meaningful sensitivity difference (10%) was poor (p = 0.09). The specificity was reduced to 46% (p < 0.01) in women on estrogen therapy. In women taking estrogen plus progesterone, specificity was 80%. CONCLUSIONS: Our results suggest that estrogen increases the false positive rate of the stress ECG. This decreased specificity is countered by co-administration of progesterone. Nonetheless, because the sensitivity of the stress ECG is only 50% to 57% in postmenopausal women, women at risk should have imaging in conjunction with stress for the optimal detection of CAD.

Myocardial perfusion imaging following percutaneous coronary intervention: the importance of restenosis, disease progression, and directed reintervention.

Percutaneous coronary intervention (PCI) has become a mainstay in the treatment of patients with coronary artery disease. Currently, more than one million coronary angioplasty and stent implantation procedures are performed annually. Although increasingly complex lesions and higher risk patients are being successfully treated percutaneously, restenosis and disease progression continue to cause significant morbidity. Restenosis occurs in approximately one-third of patients, one-half of who remain asymptomatic, while disease progression occurs at rates approaching 7% per year. Despite technological advances, unadjusted mortality rates have actually increased since the mid-1980s, and the current annual risk of a major adverse cardiac event following PCI is 5% to 7%. Although randomized clinical trials are needed to more definitively show a benefit, when performed six or more months following PCI, myocardial perfusion imaging reliably identifies patients most at risk of a poor long-term outcome. Directed reintervention can have a salutary impact on the prognosis of these patients. In view of recent data showing a positive impact of imaging and reintervention in patients after PCI, current guidelines should be reassessed.

Augmentation of myocardial blood flow in hypertensive heart disease by angiotensin antagonists: a comparison of lisinopril and losartan.

OBJECTIVES: The goal of this study was to compare myocardial perfusion reserve (MPR) before and after long-term treatment with lisinopril and losartan in patients with hypertension and left ventricular hypertrophy (LVH). BACKGROUND: Studies have suggested that treatment with angiotensin-converting enzyme inhibitors (ACEIs) improves MPR in patients with hypertension by potentiating endogenous bradykinins. Because angiotensin receptor blockers (ARBs) lack a direct effect on bradykinins, we hypothesized that they may not improve MPR. METHODS: We measured pre- and post-treatment myocardial blood flow (MBF) by positron emission tomography in 17 patients (lisinopril: 9 patients, losartan: 8 patients) with hypertension and LVH at baseline and after coronary vasodilation with intravenous dipyridamole. In addition, we measured rest and hyperemic blood flow in eight normotensive controls. RESULTS: Post-treatment maximal coronary blood flow and MPR in the lisinopril group increased significantly compared with pretreatment values (3.5 +/- 1.2 vs. 2.6 +/- 1.1 ml/min/g, p = 0.02; 3.7 +/- 1.1 vs. 2.4 +/- 1 ml/min/g, respectively, p = 0.002, respectively). Post-treatment hyperemic flow in the patients treated with lisinopril was not significantly different from corresponding measurements in controls (3.5 +/- 1.2 vs. 3.9 +/- 1 ml/min/g, respectively, p = NS). In the patients treated with losartan, there was no difference between pre- and post-treatment MBF values and MPR. CONCLUSIONS: Myocardial perfusion reserve and maximal coronary flow improved in asymptomatic patients with hypertension-induced LVH after long-term treatment with lisinopril but not with losartan. Thus, ACEIs, but not ARBs, might be effective in repairing the coronary microangiopathy associated with hypertension-induced LVH.

Assessment of myocardial viability.

The prevalence of left ventricular (LV) dysfunction and resultant congestive heart failure is increasing. Patients with this condition are at high risk for cardiac death and usually have significant limitations in their lifestyles. Although there have been advances in medical therapy resulting in improved survival and well being, the best and most definitive therapy, when appropriate, is revascularization. In the setting of coronary artery disease, accounting for approximately two thirds of cases of congestive heart failure, LV dysfunction often is not the result of irreversible scar but rather caused by impairment in function and energy use of still viable-myocytes, with the opportunity for improved function if coronary blood flow is restored. Patients with LV dysfunction who have viable myocardium are the patients at highest risk because of the potential for ischemia but at the same time benefit most from revascularization. It is important to identify viable myocardium in these patients, and radionuclide myocardial scintigraphy is an excellent tool for this. Single-photon emission computed tomography perfusion scintigraphy, whether using thallium-201, Tc-99m sestamibi, or Tc-99m tetrofosmin, in stress and/or rest protocols, has consistently been shown to be an effective modality for identifying myocardial viability and guiding appropriate management. Metabolic imaging with positron emission tomography radiotracers frequently adds additional information and is a powerful tool for predicting which patients will have an improved outcome from revascularization, including some patients referred instead for cardiac transplantation. Other noninvasive modalities, such as stress echocardiography, also facilitate the assessment of myocardial viability, but there are advantages and disadvantages compared with the nuclear techniques. Nuclear imaging appears to require fewer viable cells for detection, resulting in a higher sensitivity but a lower specificity than stress echocardiography for predicting post-revascularization improvement of ventricular function. Nevertheless, it appears that LV functional improvement may not always be necessary for clinical improvement. Future directions include use of magnetic resonance imaging, as well as larger, multicenter trials of radionuclide techniques. The increasing population of patients with LV dysfunction, and the increased benefit afforded by newer therapies, will make assessment of myocardial viability even more essential for proper patient management.

Stability of right and left ventricular ejection fractions and volumes after heart transplantation.

BACKGROUND: The long-term stability of right ventricular (RV) and left ventricular (LV) volume and function after heart transplantation has not been well characterized. Accordingly, the objective of this study was to assess time- and rejection-dependent changes in RV and LV function and volume after cardiac transplantation by means of a recently validated 3-dimensional tomographic equilibrium radionuclide ventriculography approach. METHODS: A total of 71 consecutive patients (age, mean +/- SD, 57 +/- 12 years; 62 men; 9 women) were studied 5 +/- 4 years (range 1--16 years) after heart transplantation. The mean frequency of >Grade 2 rejection was 1.7 +/- 1.8 episodes (range 0--7 episodes). RV and LV ejection fraction (EF) and end-diastolic volume (EDV) in transplant patients were compared with data from 34 subjects at low likelihood for coronary artery disease. RESULTS: No significant differences in RV or LV EF or EDV compared with controls were observed (RV EF=54 +/- 9 vs 53 +/- 9; RV EDV [ml]=109 +/- 35 vs 120 +/- 32; LV EF=72 +/- 8 vs 73 +/- 9; and LV EDV [ml]=108 +/- 28 vs 98 +/- 20 for controls and patients with transplants, respectively; p=NS for all comparisons). There was no significant effect on RV or LV EF or volumes with rejection, or with time after transplantation. CONCLUSIONS: RV as well as LV EF and EDV are stable more than 1 year after heart transplantation for up to 16 years. Thus, changes in EF or EDV in the transplanted heart are abnormal and should prompt a clinical evaluation.