Cardiovascular magnetic resonance for suspected cardiac amyloidosis: where are we now?

Cardiac amyloidosis (CA) is an underdiagnosed form of restrictive cardiomyopathy leading to a rapid progression into heart failure. Evaluation of CA requires a multimodality approach making use of echocardiography, cardiac magnetic imaging (CMR), and nuclear imaging. With superior tissue characterization, high-resolution imaging, and precise cardiac assessment, CMR has emerged as a versatile tool in the workup of cardiac amyloidosis with a wide array of parameters both visual and quantitative. This includes late gadolinium enhancement patterns, T1/T2 mapping, and extracellular volume (ECV) measurement providing robust diagnostic accuracies, patient stratification, and prognostication. Recent advancements have introduced new measures able to identify early disease, track disease progression, and response to therapy positioning CMR as an instrumental imaging modality in the era of rising interest in CA screening and emerging effective therapies.

Left ventricular mass on positron emission tomography: Validation against cardiovascular magnetic resonance.

BACKGROUND: Left ventricular hypertrophy (LVH) is an important clinical finding that is independently associated with mortality and cardiovascular events. We aimed to assess the interstudy variability of LV mass quantitation between PET and CMR. METHODS: Patients who underwent both PET and CMR within 1 year were identified from prospective institutional registries. LV mass on PET was compared against LV mass on CMR using several statistical measures of agreement. RESULTS: A total of 105 patients (mean age 60 ± 14 years, 67.6% male) were included. The median (interquartile range, IQR) duration between CMR and PET was 47 (11-154) days. The median (IQR) LV mass values were 168.0 g (126.0-202.0) on CMR and 174.0 g (150.0-212.0) with PET (absolute mean difference 29.42 ± 25.3). There was a good correlation (Spearman ρ = 0.81, P < 0.001; Intraclass Correlation Coefficient 0.78, 95% CI 0.70-0.85, P < 0.001) with moderate limits of agreement (95% limits of agreement - 63.78 to 83.7.) Results were consistent, albeit with moderate correlation, in subgroups of patients with LVH, in patients with myocardial infarction, in patients with LV ejection fraction < 50%, and those with limited image quality. LV mass on PET tended to be underestimated at high values compared to CMR. CONCLUSION: We demonstrate good correlation and reproducibility of LV mass quantitation by PET against the reference standard of CMR across a wide range of normal and diseased hearts with a tendency of PET to underestimate mass at higher mass values.

The prognostic role of cardiac positron emission tomography imaging in patients with sarcoidosis: A systematic review.

PURPOSE: Sarcoidosis is a multi-systemic inflammatory disease of unknown etiology. Cardiac sarcoidosis (CS) has been reported in as much as 25% of patients with systemic involvement. 18Fluorodeoxyglucose (FDG) positron emission tomography (PET) has a high diagnostic sensitivity/specificity in the diagnosis of CS. The aim of this review is to summarize evidence on the prognostic role of FDG PET. METHODS: Studies were identified by searching MEDLINE from inception to October 2020. Medical subject headings (MeSH) terms for sarcoidosis; cardiac and FDG PET imaging were used. Studies of any design assessing the prognostic role of FDG PET in patients with either suspected or confirmed cardiac sarcoidosis imaging done at baseline were included. Abnormal PET was defined as abnormal metabolism (presence of focal or focal-on-diffuse uptake of FDG) OR abnormal metabolism and a perfusion defect. Studies reporting any outcome measure were included. Pooled risk ratio for the composite outcome of MACE was done. RESULTS: A total of 6 studies were selected for final inclusion (515 patients, 53.4% women, 19.8% racial minorities.) Studies were institution based, retrospective in design and enrolled consecutive patients. All were observational in nature and published in English. All studies used a qualitative assessment of PET scans (abnormal FDG uptake with or without abnormal perfusion). Two studies assessed quantitative metrics (summed stress score in segments with abnormal FDG uptake, standardized uptake value and cardiac metabolic activity.) All studies reported major adverse cardiovascular events (MACE) as a composite outcome. After a mean follow up ranging from 1.4 to 4.1 years, there were a total of 105 MACE. All studies included death (either all-cause death or sudden cardiac death) and ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation) as a component of MACE. Four of the six studies adjusted for several characteristics in their analysis. All four studies used left ventricular ejection fraction (LVEF). However, other adjustment variables were not consistent across studies. Five studies found a positive prognostic association with the primary outcome, two of which assessing right ventricular uptake. CONCLUSION: Although available evidence indicates FDG PET can be used in the risk stratification of patients with CS, our findings show further studies are needed to quantify the effect in this patient group.

Coronary artery disease in patients with human immunodeficiency virus infection.

The life expectancy of people infected with human immunodeficiency virus (HIV) is rising due to better access to combination anti-retroviral therapy (ART). Although ART has reduced acquired immune deficiency syndrome (AIDS) related mortality and morbidity, there has been an increase in non-AIDS defining illnesses such as diabetes mellitus, hypercholesterolemia and coronary artery disease (CAD). HIV is a disease marked by inflammation which has been associated with specific biological vascular processes increasing the risk of premature atherosclerosis. The combination of pre-existing risk factors, atherosclerosis, ART, opportunistic infections and coagulopathy contributes to rising CAD incidence. The prevalence of CAD has emerged as a major contributor of morbidity in these patients due to longer life expectancy. However, ART has been associated with lipodystrophy, dyslipidemia, insulin resistance, diabetes mellitus and CAD. These adverse effects, along with drug-drug interactions when ART is combined with cardiovascular drugs, result in significant challenges in the care of this group of patients. Exercise tolerance testing, echocardiography, myocardial perfusion imaging, coronary computed tomography angiography and magnetic resonance imaging help in the diagnosis of CAD and heart failure and help predict cardiovascular outcomes in a manner similar to non-infected individuals. This review will highlight the pathogenesis and factors that link HIV to CAD, presentation and treatment of HIV-patients presenting with CAD and review briefly the cardiac imaging modalities used to identify this entity and help prognosticate future outcomes.

The role of cardiac imaging in the management of non-ischemic cardiovascular diseases in human immunodeficiency virus infection.

Infection with human immunodeficiency virus (HIV) has become the pandemic of the new century. About 36.9 million people are living with HIV worldwide. The introduction of antiretroviral therapy in 1996 has dramatically changed the global landscape of HIV care, resulting in significantly improved survival and changing HIV to a chronic disease. With near-normal life expectancy, contemporary cardiac care faces multiple challenges of cardiovascular diseases, disorders specific to HIV/AIDS, and those related to aging and higher prevalence of traditional risk factors. Non-ischemic cardiovascular diseases are major components of cardiovascular morbidity and mortality in HIV/AIDS. Non-invasive cardiac imaging plays a pivotal role in the management of these diseases. This review summarizes the non-ischemic presentation of the HIV cardiovascular spectrum focusing on the role of cardiac imaging in the management of these disorders.

Prevalence and predictors of frailty in a high-income developing country: A cross-sectional study.

Background: Frailty is a state of vulnerability and a decreased physiological response to stressors. As the population ages, the prevalence of frailty is expected to increase. Thus, identifying tools and resources that efficiently predict frailty among the Saudi population is important. We aimed to describe the prevalence and predictors of frailty among Saudi patients referred for cardiac stress testing with nuclear imaging. Methods: We included 876 patients (mean age 60.3 ± 11 years, women 48%) who underwent clinically indicated cardiac nuclear stress testing between January and October 2016. Fried Clinical Frailty Scale was used to assess frailty. Patients were considered frail if they had a score of four or higher. Multivariate adjusted logistic regression models were used to determine the independent predictors of elderly frail patients. Results: In this cohort, the median age of the included patients was 61 years, and the prevalence of frailty was 40%. The frail patients were older, more frequently women, and had a higher body mass index. Additionally, frailty was associated with a higher prevalence of cardiovascular risk factors: hypertension (85% vs. 70%) and diabetes (75% vs. 60%). In a fully adjusted logistic regression model, women, hypertension, and obesity (BMI ≥ 30 kg/m2) were independent predictors of elderly frail patients. Conclusions: With the aging of the Saudi population, frailty prevalence is expected to increase. Elderly, obesity, hypertension, and female gender are risk factors of frailty. Interventions to reduce frailty should be focused on this high-risk population.

Assessment of myocardial blood flow and coronary flow reserve with positron emission tomography in ischemic heart disease: current state and future directions.

Positron emission tomography (PET) is a versatile imaging technology that allows assessment of myocardial perfusion, both at a spatially relative scale and also in absolute terms, thereby enabling noninvasive evaluation of myocardial blood flow (MBF) and coronary flow reserve (CFR). Assessment of MBF using FDA-approved PET isotopes, such as 82Rb and 13N-ammonia, has been well validated, and several software packages are currently available, thereby allowing for MBF evaluation to be incorporated into routine workflow in contemporary nuclear laboratories. Incremental diagnostic and prognostic information provided with the knowledge of MBF has the potential for widespread applications. Improving the ability to identify the true burden of obstructive epicardial coronary stenoses and allowing for noninvasive assessment of coronary micro circulatory function can be achieved with MBF assessment. On the other hand, attenuated CFR has been shown to predict adverse cardiovascular prognosis in a variety of clinical settings and patient subgroups. With expanding applications of MBF, this tool promises to provide unique insight into the integrity of the entire coronary vascular bed beyond what is currently available with relative perfusion assessment. This review intends to provide an in-depth discussion of technical and clinical aspects of MBF assessment with PET as it relates to patients with ischemic heart disease.

Cardiac magnetic resonance imaging in heart failure: where the alphabet begins!

Cardiac Magnetic Resonance Imaging has become a cornerstone in the evaluation of heart failure. It provides a comprehensive evaluation by answering all the pertinent clinical questions across the full pathological spectrum of heart failure. Nowadays, CMR is considered the gold standard in evaluation of ventricular volumes, wall motion and systolic function. Through its unique ability of tissue characterization, it provides incremental diagnostic and prognostic information and thus has emerged as a comprehensive imaging modality in heart failure. This review outlines the role of main conventional CMR sequences in the evaluation of heart failure and their impact in the management and prognosis.

Assessment of left ventricular ejection fraction using low radiation dose computed tomography.

BACKGROUND: Cardiac CT is a non-invasive modality with the ability to estimate LVEF. However, given its limited temporal resolution and radiation, there has been initial resistance to use CT to measure LVEF. Developing an accurate, fast, low radiation dose protocol is desirable. OBJECTIVE: The objective of this study is to demonstrate that a 'low radiation dose' 64 slice cardiac computed tomography (CT) protocol is feasible and can accurately measure left ventricular ejection fraction (LVEF) while delivering a radiation dose lower than radionuclide angiography (RNA). METHODS: Patients undergoing RNA were prospectively screened and enrolled to undergo a 'low-dose' 64 slice CT LVEF protocol. LVEF measures, duration of each study and radiation dose between CT and RNA were compared. RESULTS: A total of 77 patients (mean age = 61.8 ± 12.2 years and 58 men) were analyzed. The mean LVEF measured by CT and RNA were 41.9 ± 15.2% and 39.4 ± 13.9%, respectively, (P = 0.154) with a good correlation (r = 0.863). Bland-Altman plot revealed a good agreement between the CT and RNA LVEF (mean difference of -2.4). There was good agreement between CT LVEF and RNA for identifying patients with LVEF ≤30% (kappa = 0.693) and LVEF ≥50% (kappa = 0.749). The mean dose estimated effective dose for CT and RNA were 4.7 ± 1.6 and 9.5 ± 1.0 mSv, respectively. The mean CT LVEF imaging duration (4:32 ± 3:05 minutes) was significantly shorter than the RNA image acquisition time (9:05 ± 2:36 minutes; p < 0.001). CONCLUSION: The results of our study suggest that low-dose CT LVEF protocol is feasible, accurate, and fast while delivering a lower radiation dose than traditional RNA.

Appraisal of amyloidosis imaging practices in the Middle East/North Africa (PYP-MENA).

Aims: Whereas recommendations to optimize performance and yield of cardiac scintigraphy studies with bone-seeking tracers have been published, little is known about real-world adherence to these best practices, especially outside North America and Europe. Accordingly, we described imaging practices with this modality in a sample of nuclear laboratories in the Middle East/North Africa (MENA) region. Methods and results: Laboratories performing radionuclide imaging for cardiac amyloidosis in the MENA region were invited to participate in this study to describe installed camera systems, type and dose of bone-avid tracers used, imaging protocols, and criteria used for study interpretation. Out of 19 invited sites, 10 completed the survey (70% government-run; 90% accredited), sites have been involved with amyloid imaging for a median of 49 months (interquartile range 24-60). The median injected dose was 20 mCi (range 10-25), and PYP was used by 90% of sites in this sample. Planar imaging with single photon emission computed tomography (SPECT) reconstruction was performed at all sites, including seven sites that performed SPECT/CT reconstruction. Lastly, only 50% of sites relied on evidence of myocardial uptake by SPECT to confirm the diagnosis of ATTR cardiomyopathy, while the rest relied on visual assessment and heart/contralateral ratio. Conclusion: This study is the first to describe variation in imaging practices across sites in the MENA region, especially in acquisition protocols and interpretation standards. Eliminating heterogeneities identified by this study will harmonize image interpretation and reporting and will facilitate successful conduct of regional multi-centre studies.

Cardiac Morbidity and Mortality in Patients with Sarcoma: A Population-Based Study.

Background: Soft tissue sarcoma (STS) is a rare malignancy that affects soft tissues. It encompasses various subtypes and requires different treatment strategies. Doxorubicin is a commonly used anthracycline in the management of localized and metastatic STS. However, high doses of doxorubicin are associated with cardiotoxicity, which can significantly impact patients' long-term outcomes. This study aimed to evaluate doxorubicin's effect on cardiac function in patients with sarcoma and to correlate the frequency of cardiotoxicity with potential risk factors. Methods: A retrospective analysis was conducted on patients with sarcoma who were treated with doxorubicin between 2016 and 2022 at King Abdulaziz Medical City in Saudi Arabia. Patient demographic information, comorbidities, cardiac measurements, laboratory values, systemic therapy, and treatment outcomes were collected from electronic medical records. A statistical analysis was performed to assess the association between cardiotoxicity and various factors. Results: A total of 133 patients were included in the study, with a median age of 30 years. Cardiotoxicity was observed in 9% of the patients. Female patients had a significantly higher risk of developing cardiotoxicity. Patients with a higher Eastern Cooperative Oncology Group (ECOG) performance status and lower troponin I levels also had an increased risk of cardiotoxicity. However, there was no significant association between cardiotoxicity and the number of chemotherapy cycles, total cumulative dose of doxorubicin, or history of radiation. Furthermore, patients with cardiotoxicity had a higher risk of mortality. The overall survival of the patients was 18 months. Conclusion: Doxorubicin-associated cardiotoxicity is a concern for patients with sarcoma. Female patients and patients with a higher ECOG performance status are at an increased risk of developing cardiotoxicity. Careful monitoring and risk assessment are crucial for mitigating the adverse effects of doxorubicin treatment in patients with sarcoma. Future studies are warranted to validate these findings and explore preventive strategies for doxorubicin-induced cardiotoxicity in patients with sarcoma.

Best Practices in Nuclear Imaging for the Diagnosis of Transthyretin Amyloid Cardiomyopathy (ATTR-CM) in KSA: The Eagle Eyes of Local Experts.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a complex and serious form of heart failure caused by the accumulation of transthyretin amyloid protein in the heart muscle. Variable symptoms of ATTR-CM can lead to a delayed diagnosis. Recognizing the diagnostic indicators is crucial to promptly detect this condition. A targeted literature review was conducted to examine the latest international consensus recommendations on a comprehensive diagnosis of ATTR-CM. Additionally, a panel consisting of nuclear medicine expert consultants (n = 10) and nuclear imaging technicians (n = 2) convened virtually from the Kingdom of Saudi Arabia (KSA) to formulate best practices for ATTR-CM diagnosis. The panel reached a consensus on a standard diagnostic pathway for ATTR-CM, which commences by evaluating the presence of clinical red flags and initiating a cardiac workup to assess the patient's echocardiogram. Cardiac magnetic resonance imaging may be needed, in uncertain cases. When there is a high suspicion of ATTR-CM, patients undergo nuclear scintigraphy and hematologic tests to rule out primary or light-chain amyloidosis. The expert panel emphasized that implementing best practices will support healthcare professionals in KSA to improve their ability to detect and diagnose ATTR-CM more accurately and promptly. Diagnosing ATTR-CM accurately and early can reduce morbidity and mortality rates through appropriate treatment.

No cardioprotective benefit of ischemic postconditioning in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Postconditioning is a potential cardioprotective strategy that has demonstrated conflicting and variable reductions in infarct size in human trials. OBJECTIVES: To determine whether postconditioning could increase the extent of myocardial salvage in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (PPCI). METHODS: One hundred two patients (aged 57 ± 11 years; 88% male) were randomly assigned to a postconditioning or standard protocol. Cardiovascular magnetic resonance imaging was performed 3 days after PPCI to measure the volumetric extent of myocardial necrosis and the area at risk. RESULTS: With similar time-to-reperfusion (170 ± 84 minutes in the postconditioning group vs. 150 ± 70 minutes in the standard group, P = 0.22), the myocardial salvage index was not significantly different between the postconditioned group and the control group, averaging 42 ± 22% vs. 33 ± 21%, respectively (P = 0.08). Furthermore, postconditioning was not associated with a smaller infarct size compared to controls (13 ± 7 g/m(2) vs. 15 ± 8 g/m(2), respectively, P = 0.18). CONCLUSIONS: Postconditioning does not significantly increase myocardial salvage or reduce infarct size in patients with STEMI undergoing PPCI. However, the possibility of a more modest impact of postconditioning cannot be excluded with our sample size.

CT vs SPECT: CT is the first-line test for the diagnosis and prognosis of stable coronary artery disease.

Non-invasive cardiac imaging is pivotal in the diagnosis and prognosis of patients with stable CAD. Nuclear SPECT, PET, stress echocardiography and more recently cardiac magnetic resonance imaging have been utilized with excellent diagnostic accuracy. However, along with their inherent individual limitations, most modalities detect ischemia but lack the ability to define coronary anatomy or evaluate for subclinical atherosclerosis. A modality that not only accurately diagnoses obstructive CAD and also facilitates early identification of non-obstructive CAD may be of interest because it may allow for earlier aggressive risk factor modification and primary prevention. Cardiac computerized tomographic angiography (CCTA) has the potential to accurately detect or exclude luminal stenosis, as well as identify and quantify subclinical atherosclerosis in the absence if luminal narrowing. However CCTA, being a relatively a new modality, has less supporting evidence when compared to more mature modalities such as SPECT. Therefore, the question that begs to be addressed is whether CCTA can be utilized as a first line test in establishing the diagnosis and prognosis of CAD.

Atrial remodeling in newly diagnosed drug-naive hypertensive subjects.

BACKGROUND: Systemic hypertension is a major risk factor for heart disease and stroke. Data regarding temporal relationship of left atrial (LA) remodeling to onset of hypertension are sparse. We aimed to quantitate LA structural and functional remodeling in newly diagnosed hypertensive patients. METHOD: We prospectively identified 380 patients with newly diagnosed systemic hypertension naive to drug therapy, and 380 age-matched control subjects without any history or evidence of hypertension. History or evidence of prior cardiovascular events, congenital or valvular heart disease, and renal dysfunction were exclusion criteria. Prevalence of LA enlargement, LA mechanical dysfunction expressed in total emptying fraction, left ventricular (LV) diastolic dysfunction, LV hypertrophy, and their interrelationships were assessed. RESULTS: Of the 380 newly diagnosed hypertensive patients, 285 (75%) had LA enlargement, 308 (81%) had LA mechanical dysfunction, and 19 (5%) had LVH. Diastolic dysfunction was present in 334 (88%) of the patients. Compared to the controls, the hypertensive group had larger maximal, minimal, and pre-A LA volumes (all P < 0.001). Total and active LA emptying fraction were significantly reduced (both P < 0.001). Total LA emptying fraction was strongly associated with systolic blood pressure [per 10 mmHg, HR 0.94 (0.89-0.98); P < 0.001], with stepwise decrease in LA emptying fraction of 6%, 10%, and 16% from the lowest (141-150 mmHg) to the top tertile of systolic blood pressure (>160 mmHg). CONCLUSION: In this drug-naive cohort with newly diagnosed hypertension, LA structural and functional remodeling, and LV diastolic dysfunction were common findings prior to initiation of drug treatment. LVH was uncommon. Impairment of LA mechanical function was evident even in the mildly hypertensive subgroup.

Incremental prognostic value of positron emission tomography-derived myocardial flow reserve in patients with and without diabetes mellitus.

AIMS: We aimed to assess the incremental prognostic value of positron emission tomography (PET)-derived myocardial flow reserve (MFR) among patients with diabetes and those without diabetes. METHODS AND RESULTS: Consecutive patients with clinically indicated PET MPI for suspected or established coronary artery disease (CAD) were included. Myocardial blood flow (MBF) in mL/min/g was obtained from dynamic images at rest and stress, while MFR was calculated as the ratio of stress to rest MBF. Patients were followed from the date of PET imaging for the occurrence of the primary outcome (composite of all-cause death, myocardial infarction, and un-planned percutaneous coronary intervention/coronary artery bypass graft occurring more than 90 days after imaging). The final cohort consisted of 6019 patients (63% with diabetes) (mean age 61 ± 11 years, 45% female, 55% obese, 76% hypertensive, and 62% dyslipidaemia). Over half (53%) of the patients had an impaired MFR (<2). During a median follow-up of 22.6 (7.8-42.5) months, 619 patients (10%, 3.8 per 1000 person-years) experienced the primary outcome. Impaired MFR (MFR < 2) was significantly associated with the primary outcome in patients with and without diabetes (diabetes: HR 1.8, 95% CI 1.4-2.3, P < 0.001; no diabetes: 1.4, 95% CI 1.0-2.1, P = 0.046). There was no interaction between diabetes status and MFR (P = 0.234). Results were consistent across subgroups of patients with no CAD and normal perfusion study. CONCLUSION: PET-derived MFR has a strong independent and incremental prognostic role in patients with diabetes and those without diabetes.

Successful Long-Term Anticoagulation with Low Molecular Weight Heparin in a Patient with Mechanical Mitral Valve and Atrial Flutter.

Mechanical heart valves are associated with high risk of thrombosis and thromboembolic complications. Vitamin K antagonist is the only approved oral medication for the anticoagulation in cases of mechanical heart valves. This poses a challenge in cases where vitamin K antagonists are contraindicated. Although temporary anticoagulation with low molecular weight heparin is common among pregnant patients with mechanical heart valves, data about long term anticoagulation with low molecular weight heparin is limited. We report a successful long-term anticoagulation with low molecular weight heparin in a patient with mechanical mitral valve and atrial flutter.