Poor outcome among patients undergoing myocardial perfusion imaging with intermediate-zone troponin.

BACKGROUND: Intermediate zone troponin elevation is defined as one to five times the upper limit of normal. Approximately half the patients presenting with chest pain to the emergency department have initial intermediate zone troponin. OBJECTIVES: We aimed to investigate the long-term outcome of patients hospitalized with chest pain and intermediate zone troponin elevation. METHODS: We investigated 8269 patients hospitalized in a tertiary center with chest pain. All patients had serial measurements of troponin during hospitalization. Patients were divided into three groups based on their initial troponin levels: negative troponin (N = 6112), intermediate zone troponin (N = 1329) and positive troponin (N = 828). All patients underwent myocardial perfusion imaging (MPI) as part of the initial evaluation. RESULTS: Mean age of the study population was 68 ± 11, of whom 36% were women. Patients with an intermediate zone troponin were older, more likely to be males, and with significantly more cardiovascular co-morbidities. Multivariate analysis adjusted for age, gender, cardiovascular risk factors, and abnormal MPI result found that patients with intermediate zone troponin had a 70% increased risk of re-hospitalization at 1 year (HR 1.70, 95%CI 1.48-1.96, p-value < 0.001) and 5.3 times higher risk of total mortality at 1-year (HR 5.33, 95%CI 3.65-7.78, p-value < 0.001). sub-group analysis found that among the intermediate zone troponin group, patients with double intermediate zone troponin had the poorest outcome. CONCLUSIONS: Intermediate zone troponin elevation is an independent risk factor associated with adverse outcomes and therefore patients with an initial value in this range should be closely monitored and aggressively managed.

Early post-stress decrease in cardiac performance by impedance cardiography and its relationship to the severity and extent of ischemia by myocardial perfusion imaging.

BACKGROUND: While single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a well-established noninvasive procedure for the evaluation of patients with coronary artery disease (CAD), it is unable to detect the presence of, or underestimates the extent of CAD in certain patients. We aimed to show that a bio-impedance device can detect early post-stress changes in several hemodynamic parameters, thereby serving as a potential marker for the presence of significant ischemia. METHODS: Prospectively enrolled patients, referred to our Medical Center for clinically-indicated MPI, underwent testing using a Non-Invasive Cardiac System (NICaS) before and immediately after exercise. The differences between rest and stress hemodynamic parameters were compared with the severity and extent of myocardial ischemia by MPI. The study included 198 patients; mean age was 62 years, 26% were women, 54% had hypertension, and 29% diabetes mellitus. Of them, 188 patients had ≤10%, and 10 had > 10% of myocardial ischemia. RESULTS: In the first group, there was a significantly greater increase in post-exercise stroke index, stroke work index, cardiac index and cardiac power index (19.2, 29.1, 90.5 and 107%, respectively) compared with the second group (- 2.7, 3.8, 43.7 and 53.5%, respectively), as well as a significantly greater decrease in total peripheral resistance index (- 38.7% compared with - 16.3%), with corresponding p values of 0.015, 0.017, 0.040, 0.016, and < 0.001, respectively. CONCLUSIONS: Our data suggest that immediate post-stress changes in several hemodynamic parameters, detected by the NICaS, can be used as an important adjunct to SPECT MPI for the early detection of myocardial ischemia.

Evaluation of Patients with Acute Chest Pain Using SPECT Myocardial Perfusion Imaging: Prognostic Implications of Mildly Abnormal Scans.

BACKGROUND: While patients presenting to emergency departments (ER) with chest pain are increasingly managed in chest pain units (CPU) that utilize accelerated diagnostic protocols for risk stratification, such as single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), data are lacking regarding the prognostic implications of mildly abnormal scans in this population. OBJECTIVES: To evaluate the prognostic implications of mildly abnormal SPECT MPI results in patients with acute chest pain. METHODS: Of the 3753 chest pain patients admitted to the CPU at the Leviev Heart Center, Sheba Medical Center 1593 were further evaluated by SPECT MPI. Scans were scored by extent and severity of stress-induced perfusion defects, with 1221 patients classified as normal, 82 with myocardial infarction without ischemia, 236 with mild ischemia, and 54 with more than mild ischemia. Mild ischemia patients were further classified to those who did and did not undergo coronary angiography within 7 days. RESULTS: Mild ischemia patients who underwent coronary angiography were more likely to be male (92% vs. 81%, P = 0.01) and to have left anterior descending ischemia (67% vs. 42%, P = 0.004). After 50 months, these patients returned less often to the ER with chest pain (53% vs. 87%, P < 0.001) and had a lower combined endpoint of acute coronary syndrome and death (8% vs. 16%, P < 0.001). CONCLUSIONS: Compared to patients with chronic stable angina, patients presenting with acute chest pain exhibiting mildly abnormal SPECT MPI findings should perhaps undergo a more aggressive diagnostic and therapeutic approach.

A novel heart rate variability algorithm for the detection of myocardial ischemia: pilot data from a prospective clinical trial.

BACKGROUND: Heart rate variability (HRV) analysis has been shown to be a predictor of sudden cardiac death and all-cause mortality in patients with cardiac disease. OBJECTIVES: To examine whether newer HRV analysis algorithms, as used by the HeartTrends device, are superior to exercise stress testing (EST) for the detection of myocardial ischemia in patients without known coronary artery disease (CAD). METHODS: We present pilot data of the first 100 subjects enrolled in a clinical trial designed to evaluate the yield of short-term (1 hour) HRV testing for the detection of myocardial ischemia. The study population comprised subjects without known CAD referred to a tertiary medical center for EST with single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). All patients underwent a 1 hour electrocardiographic acquisition for HRV analysis with a HeartTrends device prior to ESTwith MPI. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) were calculated for EST and HRV analysis, using MPI as the gold standard for the non-invasive detection of myocardial ischemia. RESULTS: In this cohort 15% had a pathologic MPI result. HRV analysis showed superior sensitivity (85%), PPV (50%) and NPV (97%) as compared to standard EST (53%, 42%, 90%, respectively), while the specificity of the two tests was similar (86% and 85%, respectively). The close agreement between HRV and MPI was even more pronounced among patients > 65 years of age. CONCLUSIONS: Our pilot data suggest that the diagnostic yield of the novel HeartTrends HRV algorithm is superior to conventional EST for the non-invasive detection of myocardial ischemia.

Comparison of the usefulness of heart rate variability versus exercise stress testing for the detection of myocardial ischemia in patients without known coronary artery disease.

Heart rate variability (HRV) has been shown to be attenuated in patients with coronary artery disease (CAD) and may, therefore, be possibly used for the early detection of myocardial ischemia. We aimed to evaluate the diagnostic yield of a novel short-term HRV algorithm for the detection of myocardial ischemia in subjects without known CAD. We prospectively enrolled 450 subjects without known CAD who were referred to tertiary medical centers for exercise stress testing (EST) with single-photon emission computed tomography myocardial perfusion imaging (MPI). All subjects underwent 1-hour Holter testing with subsequent HRV analysis before EST with MPI. The diagnostic yield of HRV analysis was compared with EST, using MPI as the gold standard for the noninvasive detection of myocardial ischemia. All subjects had intermediate pretest probability for CAD. Mean age was 62 years, 38% were women, 51% had hypertension, and 25% diabetes mellitus. HRV analysis showed superior sensitivity (77%) compared with standard EST (27%). After multivariate adjustment, HRV was independently associated with an 8.4-fold (p <0.001) increased likelihood for the detection of myocardial ischemia by MPI, whereas EST did not show a statistically significant association with a positive MPI (odds ratio 2.1; p = 0.12). Of subjects who were referred for subsequent coronary angiography, the respective sensitivities of HRV and EST for the detection of significant CAD were 73% versus 26%. Our data suggest that HRV can be used as an important noninvasive technique for the detection of myocardial ischemia in subjects without known CAD, providing superior sensitivity to conventional EST in this population.

The structural effect of the E148Q MEFV mutation on the pyrin protein: a study using a quantum chemistry model.

BACKGROUND: Familial Mediterranean fever (FMF) is a recessively inherited disease with a variety of clinical presentations. The disease is associated with mutations in the FMF gene (MEFV), which encodes for the pyrin protein. The role of the E148Q pyrin mutation in the FMF phenotype remains inconclusive, and some authors even view it as a disease-insignificant polymorphism. The calculated change imposed by this mutation on pyrin structure may help to understand the role of this mutation. OBJECTIVES: To calculate the relative electrochemical effect of the E148Q mutation on the structure of pyrin protein. METHODS: The electronic properties of the wild-type pyrin molecule and its common mutated forms were computed for the full-length molecule and its segments, encoded by exons 2 and 10, using the HyperChem 7.5 program with one of the molecular mechanical methods (MM+). The change in the structure of the molecule, expressed as a change in energy gain, conferred by the mutations was determined. RESULTS: The E148Q mutation caused deviation from the wildtype pyrin segment encoded by exon 2 by 1.15% and from the whole pyrin molecule by 0.75%, which was comparable to the R202Q mutation and less than the M694V mutation which caused a deviation from the wild-type structure of the whole pyrin molecule by 1.5%. CONCLUSIONS: A quantum chemistry-based model suggests that the structural effect of the E148Q mutation is indeed low but not zero.

[Clostridium difficile-associated diarrhea: causes and relationship to reactive arthritis].

We present a patient treated with methotrexate (MTX] for rheumatoid arthritis, in whom clostridium difficile-associated colitis has developed, without preceding antibiotic treatment. Two weeks later, the patient was admitted with knee arthritis. Reactive arthritis was diagnosed and treated successfully with the naproxen. The article discusses risk factors for Clostridium difficile-associated diarrhea [CDAD] other than antibiotics, and the relation of this pathogen to the development of reactive arthritis. It seems to be the first report of the association of MTX treatment with CDAD.

[Aortic atheroma and splenic emboli].

The association between atheroma of the thoracic aorta and systemic embolization to the brain and other organs was discovered in the early 1990s in concordance with the improvement in the trans-esophageal echocardiography technique. The optimal treatment for secondary prevention of recurrent emboli is controversial, since the results of several studies differ and even contradict one another. In this article, the authors describe a man with splenic infarct, originating from a mobile descending aortic plaque. The cLinical approach for prevention of recurrent emboli is discussed, including the surgical and medical treatment options, and the literature on that subject is reviewed. Due to the absence of guidelines for optimal treatment in these cases and the Lack of conclusive randomized trials, the chosen treatment should be individualized, based on the characteristics of the plaque and other risk factors of each patient.

[Ammonia as a cause for hepatic encephalopathy].

In a patient with cirrhosis of the liver, associated with hepatitis B virus, who was admitted for confusion and acute elevation of liver enzymes, a diagnosis of hepatic encephalopathy was made. A serum ammonia level of 54 (normal less than 33) microgram/liter, supported the diagnosis, but puzzled the medical staff regarding the possibility that ammonia may directly induce the confusion. While it is widely accepted that the ammonia level is a marker that usually parallels the amount of toxins and metabolites that bypasses the liver, its role in causing brain dysfunction is debated. However, since ammonia may directly hinder the metabolism of neuro-transmitters, and drugs and treatments specifically aimed at reducing ammonia levels may minimize the time interval for recovery from the acute brain insult, it is assumed that ammonia by itself had a role in bringing about the encephalopathy manifestations in our patients and other patients with cirrhosis of the liver.

[Neurogenic pulmonary edema].

In a patient, admitted for cerebral stroke with right side hemiparesis, an acute episode of dyspnea has developed 6 hours after admission. Based on a finding of fine rales on auscultation and a chest radiogram showing congestion, a diagnosis of pulmonary edema was made. The electrocardiogram and cardiac enzymes were normal. Other routine precipitating factors were excluded, and the acute left heart failure was ascribed to the patient's stroke. Neurogenic pulmonary edema may be a result of a vast range of neurological lesions or conditions, including status epilepticus, head trauma, subdural and subarachnoid hemorrhage, brain tumors, meningitis, multiple sclerosis and ischemic stroke. This condition is probably mediated by the sympathetic system outflow, leading eventually to an increase of left atrial pressure, or to an increase in pulmonary vessel permeability. It is treated conventionally, with diuretics and after-load reduction.

[Aspirin and endoscopy].

A patient with stable anginal syndrome, on aspirin, was admitted for colonoscopy, as part of a work-up for weightloss and iron deficiency anemia. Should this patient discontinue aspirin prior to the colonoscopy? A literature review, as well as the current guidelines of the American Association for Gastrointestinal Endoscopy, did not support such an act. An Israeli physician survey, published recently, suggests an interesting attitude for this dilemma, in which the risk imposed on the patient by withdrawal of aspirin will determine whether to continue or stop the drug prior to the procedure. Such an approach may bridge the gap between the guidelines and the natural hesitation to perform minor endoscopic surgery under aspirin treatment.

[Black tongue].

In a patient with Sjogren syndrome, receiving prednisone and methotrexate, treatment with ceftriaxone was prescribed for presumed urinary tract infection. About 20 minutes from initiation of the intravenous drug administration, the patient's lips and tongue color turned black, without swelling or additional visible changes. The drug was discontinued immediately and the black color gradually disappeared within the next 24 hours. The patient recalled a similar past episode, following local anesthetic reagent injection to the gums, for tooth extraction. Black tongue may result from a fungal disease of mouth membranes, external pigment deposition, usually associated with drugs, such as bismuth preparations, and overproduction and deposition of melanin, induced by medications, such as minocin. It is assumed that ceftriaxone, herein linked to this condition for the first time, mediated the appearance of black tongue in our patient through overproduction or fast accumulation of melanin in the patient's mouth membranes.