Maria C. Ziadi

Impaired myocardial flow reserve on rubidium-82 positron emission tomography imaging predicts adverse outcomes in patients assessed for myocardial ischemia.

OBJECTIVES We evaluated the prognostic value of myocardial flow reserve (MFR) using rubidium-82 ((82)Rb) positron emission tomography (PET) in patients assessed for ischemia. BACKGROUND The clinical value of MFR quantification using (82)Rb PET beyond relative myocardial perfusion imaging remains uncertain. METHODS We prospectively enrolled 704 consecutive patients; 677 (96%) completed follow-up (median 387 days [interquartile range: 375 to 416 days]). Patients were divided into 4 groups: I, normal summed stress score (SSS) (<4) and normal myocardial flow reserve (MFR) (>2); II, normal SSS and MFR <2; III, SSS ≥4 and MFR ≥2; IV, SSS ≥4 and MFR <2. RESULTS For patients with a normal SSS and those with an abnormal SSS, there were significant differences in outcomes for hard events (cardiac death and myocardial infarction) between patients with MFR ≥2 and those with MFR <2 (I: 1.3% vs. II: 2% [p = 0.029]; III: 1.1% vs. IV: 11.4% [p = 0.05]) and for major adverse cardiac events (MACE) (p = 0.003 and p < 0.001, respectively). In the adjusted Cox model, MFR was an independent predictor of hard events (hazard ratio: 3.3; 95% confidence interval: 1.1 to 9.5; p = 0.029) and MACE (hazard ratio: 2.4, 95% confidence interval: 1.4 to 4.4, p = 0.003). The incremental prognostic value of the MFR over the SSS was demonstrated by comparing the adjusted SSS model with and without the MFR for hard events (p = 0.0197) and MACE (p = 0.002). CONCLUSIONS MFR quantified using (82)Rb PET predicts hard cardiac events and MACE independent of the SSS and other parameters. Routine assessment of (82)Rb PET-quantified MFR could improve risk stratification for patients being investigated for ischemia.

Relation Between Right Ventricular Function and Increased Right Ventricular [18F]Fluorodeoxyglucose Accumulation in Patients With Heart Failure

Background—Left heart failure is characterized by alterations in metabolic substrate utilization, and metabolic modulation may be a future strategy in the management of heart failure. Little is known about cardiac metabolism in the right ventricle and how it relates to other measures of right ventricular (RV) function. This study was designed to measure glucose metabolism in the right ventricle, as estimated by [18F]fluorodeoxyglucose (FDG) positron emission tomography imaging and to determine the relation between RV function and FDG uptake in patients with heart failure. Methods and Results—A total of 68 patients underwent cardiac [18F]FDG positron emission tomography scanning with measurement of RV FDG uptake as a standardized uptake value. Perfusion imaging was acquired at rest with rubidium-82 or [13N]ammonia. RV function was determined by equilibrium radionuclide ventriculography. Relative RV FDG uptake was determined as the ratio of RV to LV standardized uptake value. Fifty-five percent of these patients had ischemic cardiomyopathy. The mean LV and RV ejection fractions were 21±7% and 35±10%, respectively. There was a correlation between RV ejection fraction and the ratio of RV to LV FDG uptake whether the entire LV myocardium (r=−0.40, P<0.001) or LV free wall (r=−0.43, P<0.001) was used. This relation persisted in the subgroup with nonischemic cardiomyopathy (r=−0.37, P=0.04). RV FDG uptake was weakly related to increased RV systolic pressure but not related to LV size, function, or FDG uptake. The correlation between RV ejection fraction and RV/LV FDG was maintained after partial-volume correction (r=−0.68, P<0.001). Conclusions—RV dysfunction is associated with an increase in RV FDG uptake, the magnitude of which may be correlated with severity.

Effects of Short-Term Continuous Positive Airway Pressure on Myocardial Sympathetic Nerve Function and Energetics in Patients With Heart Failure and Obstructive Sleep Apnea A Randomized Study

Background— Heart failure with reduced ejection fraction and obstructive sleep apnea (OSA), 2 states of increased metabolic demand and sympathetic nervous system activation, often coexist. Continuous positive airway pressure (CPAP), which alleviates OSA, can improve ventricular function. It is unknown whether this is due to altered oxidative metabolism or presynaptic sympathetic nerve function. We hypothesized that short-term (6–8 weeks) CPAP in patients with OSA and heart failure with reduced ejection fraction would improve myocardial sympathetic nerve function and energetics. Methods and Results— Forty-five patients with OSA and heart failure with reduced ejection fraction (left ventricular ejection fraction 35.8±9.7% [mean±SD]) were evaluated with the use of echocardiography and 11C-acetate and 11C-hydroxyephedrine positron emission tomography before and ≈6 to 8 weeks after randomization to receive short-term CPAP (n=22) or no CPAP (n=23). Work metabolic index, an estimate of myocardial efficiency, was calculated as follows: (stroke volume index×heart rate×systolic blood pressure÷Kmono), where Kmono is the monoexponential function fit to the myocardial 11C-acetate time-activity data, reflecting oxidative metabolism. Presynaptic sympathetic nerve function was measured with the use of the 11C-hydroxyephedrine retention index. CPAP significantly increased hydroxyephedrine retention versus no CPAP (&Dgr;retention: +0.012 [0.002, 0.021] versus −0.006 [−0.013, 0.005] min−1; P=0.003). There was no significant change in work metabolic index between groups. However, in those with more severe OSA (apnea-hypopnea index >20 events per hour), CPAP significantly increased both work metabolic index and systolic blood pressure (P<0.05). Conclusions— In patients with heart failure with reduced ejection fraction and OSA, short-term CPAP increased hydroxyephedrine retention, indicating improved myocardial sympathetic nerve function, but overall did not affect energetics. In those with more severe OSA, CPAP may improve cardiac efficiency. Further outcome-based investigation of the consequences of CPAP is warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00756366.

Quantification of myocardial flow reserve using positron emission imaging the journey to clinical use.

“A journey of a thousand miles begins with a single step” —Lao-tzu, The Way of Lao-tzu Chinese philosopher (604 BC to 531 BC) ([1][1]) Of the many advantages of positron emission tomography (PET) imaging, its ability to quantify biological parameters is often identified as the most important

Imaging Myocardial Metabolic Remodeling

Myocardial metabolic remodeling is the process in which the heart loses its ability to utilize different substrates, becoming dependent primarily on the metabolism of a single substrate such as glucose or fatty acids for energy production. Myocardial metabolic remodeling is central to the pathogenesis of a variety of cardiac disease processes such as left ventricular hypertrophy, myocardial ischemia, and diabetic cardiomyopathy. As a consequence, there is a growing demand for accurate noninvasive imaging approaches of various aspects of myocardial substrate metabolism that can be performed in both humans and small-animal models of disease, facilitating the crosstalk between the bedside and the bench and leading to improved patient management paradigms. SPECT, PET, and MR spectroscopy are the most commonly used imaging techniques. Discussed in this review are the strengths and weaknesses of these various imaging methods and how they are furthering our understanding of the role of myocardial remodeling in cardiovascular disease. In addition, the role of ultrasound to detect the inflammatory response to myocardial ischemia will be discussed.

Cardiac Positron Emission Tomography: Current Clinical Practice

In the last two decades, the field of nuclear cardiology has experienced significant progress. The introduction of positron emission tomography (PET) imaging represented a major breakthrough that has significantly contributed to a better understanding of physiology and pathophysiology of several heart diseases. Currently, PET imaging is recognized as a well-established method to assess cardiac perfusion, function, metabolism, and viability. This article summarizes the main clinical applications of state-of-the art cardiac PET technology.

Nuclear perfusion imaging for functional evaluation of patients with known or suspected coronary artery disease: the future is now.

Nuclear imaging, with both single-photon emission computed tomography and PET, has a well-established role in the assessment of patients with known or suspected coronary artery disease. There is a large body of evidence regarding the diagnostic accuracy and prognostic value of these modalities, however, they continue to evolve rapidly with advances in camera and tracer technology, as well as changes in imaging protocols to increase lab efficiency, improve image quality and to decrease radiation exposure to patients. Nuclear imaging also provides insights into atherogenesis at a molecular level and can be combined with other imaging modalities, providing both functional and structural data and complimentary information on the presence of coronary disease and its functional implications.