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Biomedical subjects

John J Mahmarian

Publications and source records attributed to John J Mahmarian.

14 recordsLinked to original sources
PubMed2006

Noninvasive cardiac imaging in patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and the most common cause of cardiac death in young athletes in the U.S. Noninvasive imaging plays an important role in detecting the disease, understanding its pathophysiology, and selecting as well as guiding appropriate therapy. In this review, we discuss the existing methodology with emphasis on current and emerging clinical applications in patients with HCM.

Cardiomyopathy, Hypertrophic↗
PubMed2006

An initial strategy of intensive medical therapy is comparable to that of coronary revascularization for suppression of scintigraphic ischemia in high-risk but stable survivors of acute myocardial infarction.

OBJECTIVES: The purpose of this study was to determine the relative benefit of intensive medical therapy compared with coronary revascularization for suppressing scintigraphic ischemia. BACKGROUND: Although medical therapies can reduce myocardial ischemia and improve patient survival after acute myocardial infarction, the relative benefit of medical therapy versus coronary revascularization for reducing ischemia is unknown. METHODS: A prospective randomized trial in 205 stable survivors of acute myocardial infarction was made to define the relative efficacy of an intensive medical therapy strategy versus coronary revascularization for suppressing scintigraphic ischemia as assessed by serial gated adenosine Tc-99m sestamibi myocardial perfusion tomography. All patients at baseline had large total (> or =20%) and ischemic (> or =10%) adenosine-induced left ventricular perfusion defects and an ejection fraction > or =35%. Imaging was performed during 1 to 10 days of hospital admission and repeated in an identical fashion after optimization of therapy. Patients randomized to either strategy had similar baseline demographic and scintigraphic characteristics. RESULTS: Both intensive medical therapy and coronary revascularization induced significant but comparable reductions in total (-16.2 +/- 10% vs. -17.8 +/- 12%; p = NS) and ischemic (-15 +/- 9% vs. -16.2 +/- 9%; p = NS) perfusion defect sizes. Likewise, a similar percentage of patients randomized to medical therapy versus coronary revascularization had suppression of adenosine-induced ischemia (80% vs. 81%; p = NS). CONCLUSIONS: Sequential adenosine sestamibi myocardial perfusion tomography can effectively monitor changes in scintigraphic ischemia after anti-ischemic medical or coronary revascularization therapy. A strategy of intensive medical therapy is comparable to coronary revascularization for suppressing ischemia in stable patients after acute infarction who have preserved LV function.

Adenosine↗
PubMed2006

A multinational study to establish the value of early adenosine technetium-99m sestamibi myocardial perfusion imaging in identifying a low-risk group for early hospital discharge after acute myocardial infarction.

OBJECTIVES: The purpose of this study was to determine whether gated adenosine Tc-99m sestamibi single-photon emission computed tomography (ADSPECT) could accurately define risk and thereby guide therapeutic decision making in stable survivors of acute myocardial infarction (AMI). BACKGROUND: Controversy continues as to the role of noninvasive stress imaging in stratifying risk early after AMI. METHODS: The INSPIRE (Adenosine Sestamibi Post-Infarction Evaluation) trial is a prospective multicenter trial which enrolled 728 clinically stable survivors of AMI who had gated ADSPECT within 10 days of hospital admission and subsequent 1-year follow-up. Event rates were assessed within prospectively defined INSPIRE risk groups based on the adenosine-induced left ventricular perfusion defect size, extent of ischemia, and ejection fraction. RESULTS: Total cardiac events/death and reinfarction significantly increased within each INSPIRE risk group from low (5.4%, 1.8%), to intermediate (14%, 9.2%), to high (18.6%, 11.6%) (p < 0.01). Event rates at 1 year were lowest in patients with the smallest perfusion defects but progressively increased when defect size exceeded 20% (p < 0.0001). The perfusion results significantly improved risk stratification beyond that provided by clinical and ejection fraction variables. The low-risk INSPIRE group, comprising one-third of all enrolled patients, had a shorter hospital stay with lower associated costs compared with the higher-risk groups (p < 0.001). CONCLUSIONS: Gated ADSPECT performed early after AMI can accurately identify a sizeable low-risk group who have a <2% death and reinfarction rate at 1 year. Identifying these low-risk patients for early hospital discharge may improve utilization of health care resources at considerable cost savings.

Adenosine↗
PubMed2005

Initial clinical experience with regadenoson, a novel selective A2A agonist for pharmacologic stress single-photon emission computed tomography myocardial perfusion imaging.

OBJECTIVES: Regadenoson, a selective A2A adenosine receptor agonist, was evaluated for tolerability and effectiveness as a pharmacological stress agent for detecting reversible myocardial hypoperfusion when combined with single-photon emission computed tomography (SPECT). BACKGROUND: Adenosine and dipyridamole are nonselective adenosine agonists currently used as pharmacologic stressors. Despite proven safety, these agents often cause undesirable side effects and require a continuous infusion. METHODS: This Phase II, multicenter, open-label trial was conducted in 36 patients who had demonstrated ischemia on a 6-min adenosine SPECT imaging study within the previous 2 to 46 days. Patients received regadenoson as a rapid intravenous bolus dose of 400 microg (n = 18) or 500 microg (n = 18). The radiopharmaceutical was then delivered within one minute. The SPECT images were acquired in a standard manner and uniformly processed at a central laboratory. Regadenoson and adenosine studies were presented in random order and interpreted blindly with a 17-segment model by three observers. Additionally, quantitative analysis was performed with 4D-MSPECT software (University of Michigan, Ann Arbor, Michigan). RESULTS: Overall agreement for the presence of reversible hypoperfusion was 86%. The 400-mug dose was better tolerated. Overall, regadenoson was well-tolerated; side effects (e.g., chest discomfort, flushing, dyspnea) were generally mild in severity and self-limiting. High-grade atrioventricular block and bronchospasm were not observed. CONCLUSIONS: Regadenoson is well-tolerated and seems as effective as adenosine for detecting and quantifying the extent of hypoperfusion observed with SPECT perfusion imaging. Phase III clinical trials are now underway, given the promise of regadenoson's reduced side effects and simplicity of bolus administration.

Adenosine↗
PubMed2005

Percent change in B-type natriuretic peptide levels during treadmill exercise as a screening test for exercise-induced myocardial ischemia.

BACKGROUND: Myocardial ischemia leads to changes in regional wall stress. Induction of ischemia during a treadmill exercise, although brief, may lead to transient elevation in the plasma level of B-type natriuretic peptide (BNP) from baseline levels, which could serve as a biochemical marker of myocardial ischemia. METHODS: Sixty subjects (mean age 57, 41 men) undergoing myocardial single-photon emission computed tomography (SPECT) in conjunction with Bruce protocol treadmill exercise for evaluation of chest pain or screening for ischemia had their BNPs measured (Triage Biosite Test) at baseline, immediately postexercise, and 10 to 15 minutes after exercise. RESULTS: Of the 60 patients, 10 had ischemic perfusion defects by SPECT (mean 14%, range 5%-37%). In patients with no evidence of ischemia, median BNP level at baseline was 15.05 pg/mL (interquartile range 7-37.7), increased significantly immediately postexercise median level (34.7 pg/mL [14.9-67.6]), and decreased toward baseline levels within 10 to 15 minutes postexercise (20.3 pg/mL [8.6-48.5], analysis of variance P < .001). This transient rise in BNP level during exercise was also observed in patients with ischemia but was more pronounced. Percent change in BNP level from baseline for each minute of exercise was significantly higher in patients with evidence of ischemia compared with those without (14% +/- SEM 2.3 vs 7% +/- SEM 1.2, P = .014). Patients with and without ischemia did not differ in age, exercise time, peak systolic or diastolic blood pressure, peak heart rate, or other baseline characteristics. A > 10% change in BNP level from rest per minute of exercise had a sensitivity of 80%, a specificity of 71%, and a negative predictive value of 92% to detect reversible ischemia by SPECT. CONCLUSION: Transient elevation in BNP occurs during treadmill exercise and is more pronounced in patients with ischemia. B-type natriuretic peptides may therefore be used in combination with treadmill exercise for the evaluation of coronary artery disease.

Exercise Test↗
PubMed2003

A randomized, double-blind, placebo-controlled trial of Ad5FGF-4 gene therapy and its effect on myocardial perfusion in patients with stable angina.

OBJECTIVES: The primary objective of this study was to determine whether intracoronary administration of the adenoviral gene for fibroblast growth factor (Ad5FGF-4) can improve myocardial perfusion compared with placebo. BACKGROUND: Animal studies and observational clinical studies have shown improvement in perfusion of the ischemic myocardium using genes encoding angiogenic growth factors; however, randomized, double-blind data in humans are lacking. METHODS: We performed a randomized, double-blind, placebo-controlled trial of intracoronary injection of 10(10) adenoviral particles containing a gene encoding fibroblast growth factor (Ad5FGF-4) to determine the effect on myocardial perfusion. Fifty-two patients with stable angina and reversible ischemia comprising >9% of the left ventricle on adenosine single-photon emission computed tomography (SPECT) imaging were randomized to gene therapy (n = 35) or placebo (n = 17). Clinical follow-up was performed, and 51 (98%) patients underwent a second adenosine SPECT scan after 8 weeks. RESULTS: Overall (n = 52), the mean total perfusion defect size at baseline was 32.4% of the left ventricle, with 20% reversible ischemia and 12.5% scar. At eight weeks, Ad5FGF-4 injection resulted in a significant reduction of ischemic defect size (4.2% absolute, 21% relative; p < 0.001) and placebo-treated patients had no improvement (p = 0.32). Although the change in reversible perfusion defect size between Ad5FGF-4 and placebo was not significant (4.2% vs. 1.6%, p = 0.14), when a single outlier was excluded a significant difference was observed (4.2% vs. 0.8%, p < 0.05). Ad5FGF-4 was well tolerated and did not result in any permanent adverse sequelae. CONCLUSIONS: Intracoronary injection of Ad5FGF-4 showed an encouraging trend for improved myocardial perfusion; however, further studies of therapeutic angiogenesis with Ad5FGF-4 will be necessary.

Adenosine↗
PubMedDate not supplied

Clinical value of attenuation correction in stress-only Tc-99m sestamibi SPECT imaging.

BACKGROUND: Attenuation artifact remains a substantial limitation to confident interpretation of images and reduces laboratory efficiency by requiring comparison of stress and rest image sets. Attenuation-corrected stress-only imaging has the potential to ameliorate these limitations. METHODS AND RESULTS: Ten experienced nuclear cardiologists independently interpreted 90 stress-only electrocardiography (ECG)-gated technetium 99m sestamibi images in a sequential fashion: myocardial perfusion imaging (MPI) alone, MPI plus ECG-gated data, and attenuation-corrected MPI with ECG-gated data. Images were interpreted for diagnostic certainty (normal, probably normal, equivocal, probably abnormal, abnormal, and perceived need for rest imaging). With stress MPI data alone, only 37% of studies were interpreted as definitely normal or abnormal, with a very high perceived need for rest imaging (77%). The addition of gated data did not alter the interpretations. However, attenuation-corrected data significantly increased the number of studies characterized as definitely normal or abnormal (84%, P <.005) and significantly reduced the perceived need for rest imaging (43%, P <.005). These results were confirmed by use of a nonsequential consensus interpretation of three readers. CONCLUSION: Attenuation correction applied to studies with stress-only Tc-99m ECG-gated single photon emission computed tomography images significantly increases the ability to interpret studies as definitely normal or abnormal and reduces the need for rest imaging. These findings may improve laboratory efficiency and diagnostic accuracy.

Adult↗
PubMedDate not supplied

Adenosine sestamibi SPECT post-infarction evaluation (INSPIRE) trial: A randomized, prospective multicenter trial evaluating the role of adenosine Tc-99m sestamibi SPECT for assessing risk and therapeutic outcomes in survivors of acute myocardial infarction.

BACKGROUND: Preliminary studies indicate that adenosine myocardial perfusion single photon tomography (SPECT) can safely and accurately stratify patients into low and high risk groups early after acute myocardial infarction (AMI). METHODS AND RESULTS: INSPIRE is a prospective, randomized multicenter trial which enrolled 728 clinically stable survivors of AMI. Following baseline adenosine sestamibi gated SPECT, patients were classified as low, intermediate or high risk based on the quantified total and ischemic left ventricular (LV) perfusion defect size (PDS). A subset of high risk patients with a LV ejection fraction > or =35% were randomized to a strategy of either intensive medical therapy or coronary revascularization. Adenosine SPECT was repeated at 6-8 weeks to determine the relative effects of anti-ischemic therapies on total and ischemic PDS (primary endpoint). All patients were followed for one year. The baseline demographic, clinical and scintigraphic characteristics of the study population are presented. Adenosine SPECT was performed within 1 day of admission in 12% of patients and in 64% by Day 4. CONCLUSION: The unique study design features of INSPIRE will further clarify the role of adenosine sestamibi SPECT in defining initial patient risk after AMI and in monitoring the benefits of intensive anti-ischemic therapies.

Adenosine↗
PubMedDate not supplied

Prognostic value of quantitative stress myocardial perfusion imaging in unstable angina patients with negative cardiac enzymes and no new ischemic ECG changes.

BACKGROUND: Limited data are available on the value of quantitative stress myocardial perfusion imaging (MPI) in patients with unstable angina. In this report we sought to study the long-term prognostic value of quantitative stress MPI in patients hospitalized with unstable angina with no new ischemic electrocardiographic changes and negative cardiac enzymes. METHODS AND RESULTS: The study population consisted of 136 patients who were hospitalized at the Methodist Hospital, Houston, Tex, with unstable angina and subsequently underwent MPI before discharge. Cox proportional hazards (regression) analysis was performed to identify clinical and MPI predictors of hard cardiac events (death or nonfatal myocardial infarction). During a mean follow-up of 31 +/- 17 months, 20 patients (15%) sustained either cardiac death (n = 12) or nonfatal myocardial infarction (n = 8). The significant multivariate predictors of cardiac events were the total perfusion defect size ( P = .002), the presence of reversible perfusion defects ( P = .01), and the presence of multiple perfusion defects ( P = .03). The perfusion defect size was significantly larger in patients with events than in those without events (21% +/- 20% vs 12% +/- 14%, P = .002). Kaplan-Meier analysis showed that cardiac events were much more likely to develop in patients with defects involving 15% or more of the left ventricle than in those with defects involving less than 15% of the left ventricle ( P = .003). CONCLUSIONS: In patients hospitalized with unstable angina with no new ischemic electrocardiographic changes and negative cardiac enzymes, quantitative stress MPI provides powerful prognostic information that can be used in the risk stratification of these patients.

Angina, Unstable↗
PubMedDate not supplied

Prognostic value of adenosine Tl-201 myocardial perfusion imaging after acute myocardial infarction: results of a prospective clinical trial.

BACKGROUND: We have previously shown in retrospective studies that adenosine myocardial perfusion imaging (MPI) done after acute myocardial infarction (AMI) can effectively predict the risk of future cardiac events in these patients. The objective of this study was to validate these observations in a prospective clinical trial. METHODS AND RESULTS: One hundred twenty-six stable patients underwent quantitative adenosine MPI at a mean of 4.5 +/- 2.9 days after AMI. On the basis of the MPI results, they were divided into 3 risk groups: low risk (< 20% perfusion defect), intermediate risk (> or = 20% perfusion defect with < 10% ischemia), and high risk (> or = 20% perfusion defect with > 10% ischemia). The patients were followed up for 11 +/- 5 months for the occurrence of cardiac events: death, myocardial infarction, unstable angina, or congestive heart failure. The actual event rates correlated very well with the prespecified risk groups (19% for the low-risk group, 28% for the intermediate-risk group, and 78% for the high-risk group; P < .001). The significant multivariate predictors for events were female gender (relative risk [RR], 2.90; P = .002), left ventricular ejection fraction (RR, 1.34; P = .04), and ischemic defect size (RR, 1.46; P = .001), with a global chi2 value of 26.7. CONCLUSION: This study demonstrates, in a prospectively designed clinical trial, that quantitative adenosine MPI performed soon after AMI can effectively predict the risk of future cardiac events. These findings are currently being validated in an ongoing, large, multicenter, international clinical trial.

Adenosine↗
PubMedDate not supplied

Tl-201 reinjection enhances the detection of myocardial ischemia after acute myocardial infarction.

BACKGROUND: Thallium 201 reinjection has been shown to enhance the detection of myocardial ischemia in patients with chronic coronary artery disease. However, limited data are available regarding its value in patients after acute myocardial infarction. METHODS AND RESULTS: We performed adenosine Tl-201 tomography in 126 patients in stable condition at a mean of 5 +/- 3 days after acute myocardial infarction (MI). After acquisition of redistribution images, patients were reinjected with 1 mCi of Tl-201 and reinjection images were then obtained. The stress, redistribution, and reinjection images were quantified to determine the total perfusion defect size and percent ischemia and scar. The mean age of patients was 54 +/- 10 years. Of the patients, 64% were male, 56% had Q-wave MI, 46% had anterior MI, and 34% received thrombolysis. The percent total defect size was the same on the stress-redistribution and stress-reinjection images (28.3% +/- 19.0%). The reinjection images showed an increase in ischemic defect size (14.7% +/- 13.5% vs 12.8% +/- 12.0%, P =.001) and a decrease in scar defect size (13.6% +/- 13.1% vs 15.5% +/- 13.9%, P =.001) compared with the redistribution images. The enhancement in the detection of myocardial ischemia was seen in both the infarct (P =.001) and noninfarct (P =.01) zones. CONCLUSIONS: Tl-201 reinjection enhances the detection of myocardial ischemia after acute MI compared with stress-redistribution alone.

Female↗