Echocardiographic estimation of left ventricular filling pressures in heart transplant recipients.

BACKGROUND: Echocardiographic estimation of left ventricular filling pressure in heart transplant (HTx) recipients is challenging. The ability of echocardiography to detect elevated left ventricular end-diastolic pressure (LVEDP) in HTx patients was assessed in this study. RESULTS: This descriptive cross-sectional study included 39 HTx recipients who were candidates for endomyocardial biopsy as a part of their routine post-transplantation surveillance. Doppler transthoracic echocardiography was done before the procedure, and left heart catheterization was done during the endomyocardial biopsy. Thirty-nine patients (15 female, 24 male), with a mean age of 39.6 years (range 13-70), were enrolled. A strong relation was observed between lateral E/e' and LVEDP (R = 0.64, P value < 0.001) and average E/e' and LVEDP (R = 0.6, P value < 0.001). The best cutoff value for LVEDP prediction was the average E/e' ≥ 6.8 with a sensitivity of 96.15% and specificity of 68.5% for the prediction of LVEDP more than or equal to 20 mmHg. Two predictive models comprising age, gender, and lateral E/e' or average E/e' were also proposed. A significant relationship was also found between LVEDP and left ventricular global longitudinal strain (R = - 0.31, P value < 0.01). CONCLUSIONS: Lateral E/e' was the best predictor of LVEDP. The cutoff of average E/e' had the best validity for the estimation of LVEDP. Despite the strong observed association, echocardiographic parameters cannot be considered a surrogate for invasive LVEDP measurements when seeking information about left ventricle filling pressure on heart transplant recipients.

The Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE): protocol for a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Inflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial infarction (MI), stroke and cardiovascular (CV) death, and is emerging as a novel treatment target. Trials involving anti-inflammatory medications have demonstrated outcome benefit in patients with known CV disease. In this regard, colchicine appears to hold great promise. However, there are potential drawbacks to colchicine use, as some studies have identified an increased risk of infection, and a non-significant trend for increased all-cause mortality. Thus, a more thorough understanding of the underlying mechanism of action of colchicine is needed to enable a better patient selection for this novel CV therapy. OBJECTIVE: The primary objective of the Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE) trial is to assess the effect of colchicine on vascular inflammation in the carotid arteries and ascending aorta measured with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes who have experienced a recent vascular event (acute coronary syndrome (ACS)/MI, transient ischaemic attack (TIA) or stroke). Secondary objectives include determining colchicine's effect on inflammatory biomarkers (high-sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6)). Additionally, we will assess if baseline inflammation imaging or biomarkers are associated with a treatment response to colchicine determined by imaging. Exploratory objectives will look at: (1) the difference in the inflammatory response to colchicine in patients with coronary events compared with patients with cerebral events; (2) the difference in the inflammatory response to colchicine in different vascular beds; (3) the relationship of FDG-PET imaging markers with serum biomarkers and (4) assessment of quality-of-life changes. METHODS AND DESIGN: CADENCE is a multicentre, prospective, randomised, double-blinded, placebo-controlled study to determine the effect of colchicine on arterial inflammation as assessed with imaging and circulatory biomarkers, specifically carotid arteries and aortic FDG uptake as well as hs-CRP and IL-6 among others. Patients with T2DM or pre-diabetes who have recently experienced a CV event (within 30-120 days after an ACS (ie, ST-elevation MI (STEMI) or non-STEMI)) or TIA/stroke with documented large vessel atherosclerotic disease will be randomised to treatment with either colchicine 0.6 mg oral daily or placebo. Participants will undergo baseline clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan of the ascending aorta and left and right carotid arteries. Patients will undergo treatment for 6 months and have repeat clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan at the conclusion of the study. The primary outcome will be the change in the maximum target to background ratio (TBRmax) in the ascending aorta (or carotid arteries) from baseline to follow-up on FDG PET/CT imaging. DISCUSSION: Colchicine is an exciting potential new therapy for CV risk reduction. However, its use is associated with side effects and greater understanding of its underlying mechanism of action is needed. Importantly, the current study will determine whether its anti-inflammatory action is an indirect systemic effect, or a more local plaque action that decreases inflammation. The results will also help identify patients who will benefit most from such therapy. TRIAL REGISTRATION NUMBER: NCT04181996.

Cardiac PET Myocardial Blood Flow Quantification Assessment of Early Cardiac Allograft Vasculopathy.

BACKGROUND: Positron emission tomography (PET) has demonstrated utility for diagnostic and prognostic assessment of cardiac allograft vasculopathy (CAV) but has not been evaluated in the first year after transplant. OBJECTIVES: The authors sought to evaluate CAV at 1 year by PET myocardial blood flow (MBF) quantification. METHODS: Adults at 2 institutions enrolled between January 2018 and March 2021 underwent prospective 3-month (baseline) and 12-month (follow-up) post-transplant PET, endomyocardial biopsy, and intravascular ultrasound examination. Epicardial CAV was assessed by intravascular ultrasound percent intimal volume (PIV) and microvascular CAV by endomyocardial biopsy. RESULTS: A total of 136 PET studies from 74 patients were analyzed. At 12 months, median PIV increased 5.6% (95% CI: 3.6%-7.1%) with no change in microvascular CAV incidence (baseline: 31% vs follow-up: 38%; P = 0.406) and persistent microvascular disease in 13% of patients. Median capillary density increased 30 capillaries/mm2 (95% CI: -6 to 79 capillaries/mm2). PET myocardial flow reserve (2.5 ± 0.7 vs 2.9 ± 0.8; P = 0.001) and stress MBF (2.7 ± 0.6 vs 2.9 ± 0.6; P = 0.008) increased, and coronary vascular resistance (CVR) (49 ± 13 vs 47 ± 11; P = 0.214) was unchanged. At 12 months, PET and PIV had modest correlation (stress MBF: r = -0.35; CVR: r = 0.33), with lower stress MBF and higher CVR across increasing PIV tertiles (all P < 0.05). Receiver-operating characteristic curves for CAV defined by upper-tertile PIV showed areas under the curve of 0.74 for stress MBF and 0.73 for CVR. CONCLUSIONS: The 1-year post-transplant PET MBF is associated with epicardial CAV, supporting potential use for early noninvasive CAV assessment. (Early Post Transplant Cardiac Allograft Vasculopahty [ECAV]; NCT03217786).

Incidence of Atrial Fibrillation as the Initial Manifestation of Cardiac Sarcoidosis: Insights From a Catheter Ablation Registry.

Background: Cardiac sarcoidosis (CS) is a rare form of arrhythmogenic cardiomyopathy; a delayed diagnosis can lead to significant consequences. Patients with clinically manifest CS often have minimal extracardiac involvement and thus frequently present initially to cardiology. Indeed, certain specific arrhythmic scenarios should trigger investigations for undiagnosed CS. Atrial fibrillation (AF) has been described as one of the presenting features of CS; however, the incidence of this presentation is not known. Methods: At our institution, cardiac computerized tomography is routinely performed prior to catheter ablation for AF. Noncardiac incidental findings are described by radiologists and are followed-up by interval investigations. We systematically reviewed noncardiac reports from 1574 consecutive patients in our prospective AF ablation registry. Specifically, we used text-scraping techniques to search on the following keywords: "adenopathy" and "sarcoidosis." Detailed chart review of identified cases was then performed to evaluate results of interval investigations and assess long-term outcomes. Results: Twenty of 1574 patients (1.3%) had noncardiac reports containing "adenopathy" and/or "sarcoidosis." After interval imaging and a follow-up period averaging 60 ± 35 months, only 2 patients of 1574 (0.13%) were diagnosed with CS. Four of 20 (20%) had a previous history of extracardiac sarcoidosis, and another 1 of 20 (5%) was subsequently diagnosed with extracardiac sarcoidosis. However, none of these 5 patients had evidence of cardiac involvement. Conclusions: CS is a rare finding among patients undergoing a first-time AF ablation. Our findings suggest that AF is an uncommon initial presentation of CS. Thus, investigations for CS in patients with AF are not warranted routinely, unless additional suggestive clinical features are present.

Contexte: La sarcoïdose cardiaque (SC) est une forme rare de cardiomyopathie arythmogène; un retard dans le diagnostic peut entraîner d'importantes conséquences. Les patients qui présentent une SC cliniquement manifeste ont souvent une atteinte extracardiaque minime, et consultent donc souvent d'abord en cardiologie. En effet, certains scénarios arythmiques précis devraient déclencher la recherche de signes d'une SC non diagnostiquée. La fibrillation auriculaire (FA) a été décrite comme un signe indicateur de SC; on ne connaît toutefois pas l'incidence de ce signe. Méthodologie: Dans notre établissement, la tomodensitométrie cardiaque est souvent réalisée avant une ablation par cathéter de la FA. Les découvertes non cardiaques fortuites sont décrites par les radiologues, puis font l'objet d'un suivi par des examens d'imagerie réalisés à intervalles déterminés. Nous avons systématiquement évalué les éléments non cardiaques signalés chez 1 574 patients consécutifs dans notre registre prospectif sur l'ablation de la FA. Nous avons utilisé des techniques de dépouillement du texte pour trouver les mots-clés suivants : « adenopathy ¼ (adénopathie) et « sarcoidosis ¼ (sarcoïdose). Un examen du dossier médical complet des cas retenus a été réalisé pour évaluer les résultats des examens de suivi et évaluer les résultats à long terme. Résultats: Parmi les 1 574 patients, 20 (1,3 %) présentaient des notes non cardiaques contenant les termes « adenopahy ¼ (adénopathie) ou « sarcoidosis ¼ (sarcoïdose). Après l'examen d'imagerie et une période de suivi d'une durée moyenne de 60 ±35 mois, seuls deux patients (0,13 %) ont reçu un diagnostic de SC. Quatre des 20 patients visés (20 %) présentaient des antécédents de sarcoïdose extracardiaque, et un patient sur 20 (5 %) a reçu un diagnostic de sarcoïdose extracardiaque à la suite de l'intervention. Toutefois, aucun de ces cinq patients ne montrait de signes d'atteinte cardiaque. Conclusions: La SC est une occurrence rare chez les patients qui subissent une première ablation de la FA. Nos constats indiquent que la FA est une présentation initiale peu commune de la SC. Aussi, la recherche de la SC chez les patients atteints de FA n'est pas justifiée dans une procédure de routine, à moins que d'autres caractéristiques cliniques pointant vers cette affection ne soient présentes.

NT-proBNP level as a substitute for myocardial perfusion scan in preoperative cardiovascular risk assessment in noncardiac surgery.

BACKGROUND: Preoperative cardiovascular risk assessment is one of the main principles before noncardiac surgeries. Cardiac stress imaging, such as myocardial perfusion scan (MPS), is a proposed cardiovascular risk evaluation method according to the latest guidelines. Yet, its efficacy, along with the cost-effectiveness of the method, has been questioned in previous studies. Our study aims to evaluate the utility of N-terminal pro-b-type natriuretic peptide (NT-proBNP) level measurement in predicting postoperative cardiovascular complications in candidates who have undergone an MPS before surgery and compare the results. METHODS: A cohort of 80 patients with a revised cardiac risk index score of one or more who were scheduled for moderate to high-risk noncardiac surgeries and met the criteria to undergo an MPS for risk assessment were included in the study. All of them underwent an MPS one week before surgery. Their preoperative NT-proBNP, troponin levels, and electrocardiograms were obtained one day before surgery and again on day three postoperative. The predictive efficacy of NT-proBNP levels and MPS were compared. RESULTS: Seventy-eight patients underwent surgery, three of which exhibited a rise in troponin level, six showed changes on electrocardiogram, and pulmonary edema was detected in one, three days after surgery. There was no mortality in our patients. The sensitivity and specificity of the MPS for predicting postoperative cardiovascular complications were 100% and 66%, respectively. MPS also had a positive predictive value of 20% and a negative predictive value of 100% in our study. A 332.5 pg/ml cut-off value for NT-proBNP level yielded a sensitivity of 100%, specificity of 79.2%, positive predictive value of 40%, and negative predictive value of 100%. CONCLUSIONS: Our study reveals the incremental specificity and positive predictive value of NT-proBNP level measurement in preoperative cardiovascular risk evaluation compared to MPS. Given the low feasibility, high costs, and disappointing predictive value of MPS, preoperative NT-proBNP level assessment can be substituted. This method can assist anesthesiologists and surgeons with precisely detecting at-risk patients resulting in taking proper measures to reduce the morbidity and mortality of the proposed patients before and during surgeries.

Utility of FFRCT in Patients with Chest Pain.

PURPOSE OF REVIEW: The goal of this article is to review the data supporting the use of fractional flow reserve derived from coronary computed tomography angiography (FFRCT) in patients with chest pain. REVIEW FINDINGS: Numerous clinical trials have demonstrated that the diagnostic accuracy of coronary computed tomography angiography (CCTA) can be improved with the use of FFRCT, primarily due to its superior specificity when compared to CCTA alone. This promising development may help reduce the need for invasive angiography in patients presenting with chest pain. Furthermore, some studies have indicated that incorporating FFRCT into decision-making is safe, with an FFRCT value of ≥ 0.8 being associated with favorable outcomes. While FFRCT has been shown to be feasible in patients with acute chest pain, further large-scale studies are warranted to confirm its utility. The emergence of FFRCT as a tool for the management of patients with chest pain is promising. However, potential limitations require the interpretation of FFRCT in conjunction with clinical context.

Exponential dosing to standardize myocardial perfusion image quality with rubidium-82 PET.

BACKGROUND: 82Rb PET is commonly performed using the same injected activity in all patients, resulting in lower image quality in larger patients. This study compared 82Rb dosing with exponential vs proportional functions of body weight on the standardization of myocardial perfusion image (MPI) quality. METHODS: Two sequential cohorts of N = 60 patients were matched by patient weight. Rest and dipyridamole stress 82Rb PET was performed using 0.1 MBq·kg-2 exponential and 9 MBq·kg-1 proportional dosing. MPI scans were compared qualitatively with visual image quality scoring (IQS) and quantitatively using the myocardium-to-blood contrast-to-noise ratio (CNR) and blood background signal-to-noise ratio (SNR) as a function of body weight. RESULTS: Average (min-max) patient body weight was 81 ± 18 kg (46-137 kg). Proportional dosing resulted in decreasing CNR, SNR, and visual IQS with increasing body weight (P < 0.05). Exponential dosing eliminated the weight-dependent decreases in these image quality metrics that were observed in the proportional dosing group. CONCLUSION: 82Rb PET dosing as an exponential (squared) function of body weight produced consistent stress perfusion image quality over a wide range of patient weights. Dramatically lower doses can be used in lighter patients, with the equivalent population dose shifted toward the heavier patients to standardize diagnostic image quality.

Advances in Single-Photon Emission Computed Tomography: Hardware, Software, and Myocardial Flow Reserve.

The clinical presentation of coronary artery disease (CAD) has changed during the last 20 years with less ischemia on stress testing and more nonobstructive CAD on coronary angiography. Single-photon emission computed tomography (SPECT) myocardial perfusion imaging should include the measurement of myocardial flow reserve and assessment of coronary calcium for the diagnosis of nonobstructive CAD and coronary microvascular disease. SPECT/CT systems provide reliable attenuation correction for better specificity and low-dose CT for coronary calcium evaluation. SPECT MFR measurement is accurate, well validated, and repeatable.

Dual versus single energy cardiac CT to measure extra cellular volume in cardiac amyloidosis: Correlations with cardiac MRI.

Rationale and objectives: Determine in cardiac amyloid (CA) patients, whether cardiac CT derived extracellular volume (ECV) correlates with that obtained by MRI. Perform this correlation with single (SECT) versus dual energy (DECT) CT and evaluate whether a single sample volume ECV-measure was as reliable as a global (16 segment) assessment. Materials and methods: CA patients who had undergone a clinical cardiac MRI (CMR) were recruited prospectively. SECT and DECT cardiac scans were performed. Three ECG-triggered prospective SECT scans were acquired: non-contrast, arterial-phase contrast and 5-minute delayed images. A DECT scan was performed at 7 min. Post processing was used to determine ECV. Analyses of SECT or DECT global ECV versus CMR were performed using the Pearson correlation coefficient, Bland Altman analysis and Intraclass correlation coefficient (ICC). Similar analyses were performed to examine the performance of single-segment sampling by SECT or DECT versus CMR. Results: 25 patients were recruited, mean age was 80.0 ± 7.1 years, 80 % were male, 21 patients had transthyretin- CA, 4 had light chain- CA. Correlations were close with both SECT or DECT global ECV versus CMR (r = 0.79 and 0.88 respectively, p < 0.001 for both). Reliability of both SECT and DECT to assess global ECV in comparison to CMR was good: ICC for SECT was 0.88 (95 % CI 0.73-0.95) and 0.93 (95 % CI 0.82-0.97) for DECT. For single volume sampling techniques: correlations were close with both SECT or DECT versus CMR (r = 0.60 and 0.72 respectively, p < 0.01 for both) There was no difference in ICC for SECT (0.74, 95 %CI 0.41-0.88) versus DECT (0.84, 95 % CI 0.63-0.93). Wider confidence intervals were noted for ICC with single versus global CT derived ECV assessment. Mean effective radiation dose was for SECT was 5.49 ± 8.04 mSv and 6.90 ± 3.01 mSv for DECT dual energy CT (p = 0.75). Conclusions: Global ECV values derived by both DECT or SECT correlated with those obtained by CMR and demonstrated good reliability by ICC in a population of CA patients. DECT and SECT single sampling derived ECV values also demonstrated close correlation and good reliability but the ICCs for single sampling had wider confidence intervals than global ECV assessment.

Role of nuclear cardiology in diagnosis and risk stratification of coronary microvascular disease.

Coronary flow reserve (CFR) with positron emission tomography/computed tomography (PET/CT) has an important role in the diagnosis of coronary microvascular disease (CMD), aids risk stratification and may be useful in monitoring therapy. CMD contributes to symptoms and a worse prognosis in patients with coronary artery disease (CAD), nonischemic cardiomyopathies, and heart failure. CFR measurements may improve our understanding of the role of CMD in symptoms and prognosis in CAD and other cardiovascular diseases. The clinical presentation of CAD has changed. The prevalence of nonobstructive CAD has increased to about 50% of patients with angina undergoing angiography. Ischemia with nonobstructive arteries (INOCA) is recognized as an important cause of symptoms and has an adverse prognosis. Patients with INOCA may have ischemia due to CMD, epicardial vasospasm or diffuse nonobstructive CAD. Reduced CFR in patients with INOCA identifies a high-risk group that may benefit from management strategies specific for CMD. Although measurement of CFR by PET/CT has excellent accuracy and repeatability, use is limited by cost and availability. CFR measurement with single-photon emission tomography (SPECT) is feasible, validated, and would increase availability and use of CFR. Patients with CMD can be identified by reduced CFR and selected for specific therapies.

Non-invasive diagnosis of vasospastic angina.

Vasospastic angina (VSA), or variant angina, is an under-recognized cause of chest pain and myocardial infarction, especially in Western countries. VSA leads to a declined quality of life and is associated with increased morbidity and mortality. Currently, the diagnosis of VSA relies on invasive testing that requires the direct intracoronary administration of ergonovine or acetylcholine. However, invasive vasoreactivity testing is underutilized. Several non-invasive imaging alternatives have been proposed to screen for VSA. This review aims to discuss the strengths and limitations of available non-invasive imaging tests for vasospastic angina.

Radiolabeled Thioflavin-T Derivative PET Imaging for the Assessment of Cardiac Amyloidosis.

PURPOSE OF REVIEW: Cardiac amyloidosis (CA) is an often under-recognized cause of heart failure with preserved ejection fraction. The goal of the current paper was to review imaging modalities available for detecting cardiac amyloidosis. We wished to determine what modalities are available for the diagnosis of cardiac amyloidosis and what modalities could be utilized in the future. RECENT FINDINGS: Early and delayed planar imaging of the chest currently plays a central role in the workup and diagnosis of CA. However, novel positron emission tomography (PET) tracers could play a large role in CA imaging in the future. There is an increasing body of literature supporting the use of targeted amyloid-binding PET radiotracers such as 11C-Pittsburgh compound B (11C-PIB), 18F-florbetapir, -flutemetamol, and -florbetaben for the detection of cardiac amyloid. While planar imaging currently plays a large role in the workup of CA, PET imaging could play an increasing important role in the future. The quantitative abilities of novel PET tracers could theoretically allow for the serial monitoring of patients and detection of response to therapy, and the sensitive nature of the tracers could allow for even earlier disease detection. Further work with large randomized controlled trial data is needed in the development and validation of PET tracers for cardiac amyloid and represents an exciting development within the realm of nuclear cardiology.