Early diagnosis and management of cardiac amyloidosis: A clinical perspective.

Cardiac amyloidosis multidisciplinary team (MDT). We propose the creation of a multidisciplinary team (MDT) for cardiac amyloidosis in which internal medicine physicians could take a lead role in coordinating other specialists involved in patient care. Created with BioRender.com.

Inflammation and Myocardial Blood Flow in Cardiac Sarcoidosis.

PURPOSE OF THE REVIEW: Cardiac involvement in systemic sarcoidosis or isolated cardiac sarcoidosis plays a pivotal role in the clinical manifestation and prognostication. Active-inflammatory cardiac sarcoidosis is associated with a regional impairment of coronary microvascular function that may confer further detrimental effects on myocardial function needing further characterization. RECENT FINDINGS: Clinical investigations with cardiac positron emission tomography/computed tomography in conjunction with 18F-fluorodeoxyglucose to determine myocardial inflammation and 13N-ammonia to quantify myocardial blood flow (MBF) in patients with known or suspected cardiac sarcoidosis outlined that sarcoidosis-induced myocardial inflammation was associated with adverse effects on corresponding regional coronary microvascular function. Notably, immune-suppressive treatment caused reductions in myocardial inflammation were paralleled by improvements of coronary microvascular dysfunction outlining direct adverse effect of inflammation on coronary arteriolar function. This review summarizes contributions of cardiac PET imaging in the identification and characterization of active-inflammatory cardiac sarcoidosis, its effect on coronary microvascular function, treatment responses, and prognostic implications.

Quantification of myocardial oxygen extraction fraction: A proof-of-concept study.

PURPOSE: To demonstrate a proof of concept for the measurement of myocardial oxygen extraction fraction (mOEF) by a cardiovascular magnetic resonance technique. METHODS: The mOEF measurement was performed using an electrocardiogram-triggered double-echo asymmetric spin-echo sequence with EPI readout. Seven healthy volunteers (22-37 years old, 5 females) were recruited and underwent the same imaging scans at rest on 2 different days for reproducibility assessment. Another 5 subjects (23-37 years old, 4 females) underwent cardiovascular magnetic resonance studies at rest and during a handgrip isometric exercise with a 25% of maximal voluntary contraction. Both mOEF and myocardial blood volume values were obtained in septal regions from respective maps. RESULTS: The reproducibility was excellent for the measurements of mOEF in septal myocardium (coefficient of variation: 3.37%) and moderate for myocardial blood volume (coefficient of variation: 19.7%). The average mOEF and myocardial blood volume of 7 subjects at rest were 0.61 ± 0.05 and 11.0 ± 4.3%, respectively. The mOEF agreed well with literature values that were measured by PET in healthy volunteers. In the exercise study, there was no significant change in mOEF (0.61 ± 0.06 vs 0.62 ± 0.07) or myocardial blood volume (12 ± 6% vs 13 ± 4%) from rest to exercise, as expected. CONCLUSION: The implemented cardiovascular magnetic resonance method shows potential for the quantitative assessment of mOEF in vivo. Future technical work is needed to improve image quality and to further validate mOEF measurements.

Higher incidence of vasodilator-induced left ventricular cavity dilation by PET when compared to treadmill exercise-ECHO in hypertrophic cardiomyopathy.

BACKGROUND: Vasodilator-induced transient left ventricular cavity dilation (LVCD) by positron emission tomography (PET) is associated with microvascular dysfunction in hypertrophic cardiomyopathy (HCM). Here we assessed whether HCM patients who develop LVCD by PET during vasodilator stress also develop LV cavity dilation by echocardiography (ECHO-LVCD) following exercise stress. METHODS: A retrospective analysis of cardiac function and myocardial blood flow (MBF) was conducted in 108 HCM patients who underwent perfusion-PET and exercise-ECHO as part of their clinical evaluation. We performed a head-to-head comparison of LV volumes and ejection fraction (LVEF) at rest and stress (during vasodilator stress, post-exercise), in 108 HCM patients. A ratio > 1.13 of stress to rest LV volumes was used to define PET-LVCD, and a ratio > 1.17 of stress to rest LVESV was used to define ECHO-LVCD. Patients were divided into 2 groups based on the presence/absence of PET-LVCD. MBF and myocardial flow reserve were quantified by PET, and global longitudinal strain (GLS) was assessed by ECHO at rest/stress in the two groups. RESULTS: PET-LVCD was observed in 51% (n = 55) of HCM patients, but only one patient had evidence of ECHO-LVCD (ratio = 1.36)-this patient also had evidence of PET-LVCD (ratio = 1.20). The PET-LVCD group had lower PET-LVEF during vasodilator stress, but ECHO-LVEF increased in both groups post-exercise. The PET-LVCD group demonstrated higher LV mass, worse GLS at rest/stress, and lower myocardial flow reserve. Incidence of ischemic ST-T changes was higher in the PET-LVCD group during vasodilator stress (42 vs 17%), but similar (30%) in the two groups during exercise. CONCLUSION: PET-LVCD reflects greater degree of myopathy and microvascular dysfunction in HCM. Differences in the cardiac effects of exercise and vasodilators and timing of stress-image acquisition could underlie discordance in ischemic EKG changes and LVCD by ECHO and PET, in HCM.

PET Radiopharmaceuticals for Imaging Chemotherapy-Induced Cardiotoxicity.

PURPOSE OF REVIEW: Currently, cardiotoxicity is monitored through echocardiography or multigated acquisition scanning and is defined as 10% or higher LVEF reduction. The latter stage may represent irreversible myocardium injury and limits modification of therapeutic paradigms at earliest stages. To stratify patients for anthracycline-related heart failure, highly sensitive and molecularly specific probes capable of interrogating cardiac damage at the subcellular levels have been sought. RECENT FINDINGS: PET tracers may provide noninvasive assessment of earliest changes within myocardium. These tracers are at nascent stages of development and belong primarily to (a) mitochondrial potential-targeted and (b) general ROS (reactive oxygen species)-targeted radiotracers. Given that electrochemical gradient changes at the mitochondrial membrane represent an upstream, and earliest event before triggering the production of the ROS and caspase activity in a biochemical cascade, the former category might offer interrogation of cardiotoxicity at earliest stages exemplified by PET imaging, using 18F-Mitophos and 68Ga-Galmydar in rodent models. Both categories of radiotracers may provide tools for monitoring chemotherapy-induced cardiotoxicity and interrogating therapeutic efficacy of cardio-protectants.

Comparison of two software systems for quantification of myocardial blood flow in patients with hypertrophic cardiomyopathy.

BACKGORUND: Quantification of myocardial blood flow (MBF) by positron emission tomography (PET) is important for investigation of angina in hypertrophic cardiomyopathy (HCM). Several software programs exist for MBF quantification, but they have been mostly evaluated in patients (with normal cardiac geometry), referred for evaluation of coronary artery disease (CAD). Software performance has not been evaluated in HCM patients who frequently have hyperdynamic LV function, LV outflow tract (LVOT) obstruction, small LV cavity size, and variation in the degree/location of LV hypertrophy. AIM: We compared results of MBF obtained using PMod, which permits manual segmentation, to those obtained by FDA-approved QPET software which has an automated segmentation algorithm. METHODS: 13N-ammonia PET perfusion data were acquired in list mode at rest and during pharmacologic vasodilation, in 76 HCM patients and 10 non-HCM patients referred for evaluation of CAD (CAD group.) Data were resampled to create static, ECG-gated and 36-frame-dynamic images. Myocardial flow reserve (MFR) and MBF (in ml/min/g) were calculated using QPET and PMod softwares. RESULTS: All HCM patients had asymmetric septal hypertrophy, and 50% had evidence of LVOT obstruction, whereas non-HCM patients (CAD group) had normal wall thickness and ejection fraction. PMod yielded significantly higher values for global and regional stress-MBF and MFR than for QPET in HCM. Reasonably fair correlation was observed for global rest-MBF, stress-MBF, and MFR using these two softwares (rest-MBF: r = 0.78; stress-MBF: r = 0.66.; MFR: r = 0.7) in HCM patients. Agreement between global MBF and MFR values improved when HCM patients with high spillover fractions (> 0.65) were excluded from the analysis (rest-MBF: r = 0.84; stress-MBF: r = 0.72; MFR: r = 0.8.) Regionally, the highest agreement between PMod and QPET was observed in the LAD territory (rest-MBF: r = 0.82, Stress-MBF: r = 0.68) where spillover fraction was the lowest. Unlike HCM patients, the non-HCM patients (CAD group) demonstrated excellent agreement in MBF/MFR values, obtained by the two softwares, when patients with high spillover fractions were excluded (rest-MBF: r = 0.95; stress-MBF: r = 0.92; MFR: r = 0.95). CONCLUSIONS: Anatomic characteristics specific to HCM hearts contribute to lower correlations between MBF/MFR values obtained by PMod and QPET, compared with non-HCM patients. These differences indicate that PMod and QPET cannot be used interchangeably for MBF/MFR analyses in HCM patients.

Correction to: Comparison of two software systems for quantification of myocardial blood flow in patients with hypertrophic cardiomyopathy.

The following information is missing from the Funding footnote on the first page of the published article: "This study was partly funded by NIH RO1 HL092985." The last/corresponding author is incorrectly listed on the first page of the published article: The correct name is Abraham MR.

Novel Myocardial PET/CT Receptor Imaging and Potential Therapeutic Targets.

PURPOSE OF THE REVIEW: Activation of myocardial cannabinoid type 1 receptors (CB1-R) and/or angiotensin II type 1 receptors (AT1-R) likely plays an important mechanistic role in determining the left-ventricular remodeling process in systolic heart failure. We provide an overview on novel radiotracer probes and positron emission tomography (PET)/computed tomography (CT) imaging to noninvasively probe the expression of myocardial CB1-R and/or AT1-R. RECENT FINDINGS: Recent translational investigations have demonstrated the feasibility of 11C-OMAR or 11C-KR31173 and PET/CT to image and quantify myocardial CB1-R and/or AT1-R expression, respectively. There is an increasing understanding of the mechanisms of activated myocardial CB1-R and/or AT1-R to influence the left-ventricular remodeling process in systolic heart failure in different disease entities. The review summarizes contributions of PET to image myocardial CB1-R and AT1-R expression that may have the potential to serve as a target to tailor preventive medical care in the individual patient.

Correction to: Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC.

The above position statement originally published containing errors in the author metadata; specifically, the Expert Content Reviewers-Andrew Einstein, Raymond Russell and James R. Corbett-were tagged as full authors of the paper. The article metadata has now been corrected to remove Drs. Einstein, Russell and Corbett from the author line, and the PubMed record has been updated accordingly.

Pathophysiology of ST-segment elevation myocardial infarction: novel mechanisms and treatments.

Despite major advances in mechanical and pharmacological reperfusion strategies to improve acute myocardial infarction (MI) injury, substantial mortality, morbidity, and socioeconomic burden still exists. To further reduce infarct size and thus ameliorate clinical outcome, the focus has also shifted towards early detection of MI with high-sensitive troponin assays, imaging, cardioprotection against pathophysiological targets of myocardial reperfusion injury with mechanical (ischaemic post-conditioning, remote ischaemic pre-conditioning, therapeutic hypothermia, and hypoxemia) and newer pharmacological interventions (atrial natriuretic peptide, cyclosporine A, and exenatide). Evidence from animal models of myocardial ischaemia and reperfusion also demonstrated promising results on more selective anti-inflammatory compounds that require additional validation in humans. Cardiac stem cell treatment also hold promise to reduce infarct size and negative remodelling of the left ventricle that may further improves symptoms and prognosis in these patients. This review focuses on the pathophysiology, detection, and reperfusion strategies of ST-segment elevation MI as well as current and future challenges to reduce ischaemia/reperfusion injury and infarct size that may result in a further improved outcome in these patients.

Impact of incomplete revascularization of coronary artery disease on long-term cardiac outcomes. Retrospective comparison of angiographic and myocardial perfusion imaging criteria for completeness.

BACKGROUND: Coronary revascularization in patients with coronary artery disease may be guided by coronary angiography (CA) or alternatively by ischemia on stress myocardial perfusion imaging (MPI). Which strategy leads to optimal cardiac outcomes is uncertain. METHODS: We performed a retrospective analysis of 170 patients with MPI ischemia and percutaneous coronary intervention. The primary endpoint was all-cause mortality at a mean follow-up of 47 ± 21 months; the secondary end point was the composite of deaths, nonfatal myocardial infarction, and repeat coronary revascularization (MACE). The coronary revascularization was defined as complete (CCR) or incomplete (ICR) as judged by CA criteria and by MPI ischemia matched with CA criteria. RESULTS: Nighty-two patients (54%) had ICR by CA criteria (ICR-CA) and 84 (49%) had ICR by MPI criteria (ICR-MPI). Mortality and MACE were lower in patients with CCR-MPI than with ICR-MPI (P = .048, and P = .025). Survival of patients with CCR-CA and ICR-CA was not different (P = .081). Patients with both ICR-MPI and ICR-CA had the worst survival, whereas patients with CCR-MPI and CCR-CA had the best survival (P = .047). By multivariate analysis, ICR-MPI + ICR-CA was an independent predictor of death (P = .025). CONCLUSION: Patients with ICR by MPI were at higher risk than those with CCR. Patients with both ICR by MPI and CA were at the highest risk, while patients with CCR by both MPI and CA had the best long-term event-free survival.