A Description and Safety Overview of Irreversible Electroporation for Prostate Tissue Ablation in Intermediate-Risk Prostate Cancer Patients: Preliminary Results from the PRESERVE Trial.

The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion. The primary endpoints included negative in-field biopsy and adverse event incidence, type, and severity through 12 months. At the time of analysis, the trial had completed accrual with preliminary follow-up available. Demographics, disease characteristics, procedural details, PSA responses, and adverse events (AEs) are presented. The median (IQR) age at screening was 67.0 (61.0-72.0) years and Gleason distribution 3 + 4 (80.2%) and 4 + 3 (19.8%). At 6 months, all patients with available data (n = 74) experienced a median (IQR) percent reduction in PSA of 67.6% (52.3-82.2%). Only ten subjects (8.3%) experienced a Grade 3 adverse event; five were procedure-related. No Grade ≥ 4 AEs were reported. This study supports prior findings that IRE prostate ablation with the NanoKnife System can be performed safely. Final results are required to fully assess oncological, functional, and safety outcomes.

Machine learning of ECG waveforms and cardiac magnetic resonance for response and survival after cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) can lead to marked symptom reduction and improved survival in selected patients with heart failure with reduced ejection fraction (HFrEF); however, many candidates for CRT based on clinical guidelines do not have a favorable response. A better way to identify patients expected to benefit from CRT that applies machine learning to accessible and cost-effective diagnostic tools such as the 12-lead electrocardiogram (ECG) could have a major impact on clinical care in HFrEF by helping providers personalize treatment strategies and avoid delays in initiation of other potentially beneficial treatments. This study addresses this need by demonstrating that a novel approach to ECG waveform analysis using functional principal component decomposition (FPCD) performs better than measures that require manual ECG analysis with the human eye and also at least as well as a previously validated but more expensive approach based on cardiac magnetic resonance (CMR). Analyses are based on five-fold cross validation of areas under the curve (AUCs) for CRT response and survival time after the CRT implant using Cox proportional hazards regression with stratification of groups using a Gaussian mixture model approach. Furthermore, FPCD and CMR predictors are shown to be independent, which demonstrates that the FPCD electrical findings and the CMR mechanical findings together provide a synergistic model for response and survival after CRT. In summary, this study provides a highly effective approach to prognostication after CRT in HFrEF using an accessible and inexpensive diagnostic test with a major expected impact on personalization of therapies.

The Role of Multimodality Imaging in Cardiomyopathy.

PURPOSE OF REVIEW: There has been increasing use of multimodality imaging in the evaluation of cardiomyopathies. RECENT FINDINGS: Echocardiography, cardiac magnetic resonance (CMR), cardiac nuclear imaging, and cardiac computed tomography (CCT) play an important role in the diagnosis, risk stratification, and management of patients with cardiomyopathies. Echocardiography is essential in the initial assessment of suspected cardiomyopathy, but a multimodality approach can improve diagnostics and management. CMR allows for accurate measurement of volumes and function, and can easily detect unique pathologic structures. In addition, contrast imaging and parametric mapping enable the characterization of tissue features such as scar, edema, infiltration, and deposition. In non-ischemic cardiomyopathies, metabolic and molecular nuclear imaging is used to diagnose rare but life-threatening conditions such amyloidosis and sarcoidosis. There is an expanding use of CCT for planning electrophysiology procedures such as cardioversion, ablations, and device placement. Furthermore, CCT can evaluate for complications associated with advanced heart failure therapies such as cardiac transplant and mechanical support devices. Innovations in multimodality cardiac imaging should lead to increased volumes and better outcomes.

Myocardial Blood Flow Quantified Using Stress Cardiac Magnetic Resonance After Mild COVID-19 Infection.

BACKGROUND: Severe COVID-19 infection is known to alter myocardial perfusion through its effects on the endothelium and microvasculature. However, the majority of patients with COVID-19 infection experience only mild symptoms, and it is unknown if their myocardial perfusion is altered after infection. OBJECTIVES: The authors aimed to determine if there are abnormalities in myocardial blood flow (MBF), as measured by stress cardiac magnetic resonance (CMR), in individuals after a mild COVID-19 infection. METHODS: We conducted a prospective, comparative study of individuals who had a prior mild COVID-19 infection (n = 30) and matched controls (n = 26) using stress CMR. Stress and rest myocardial blood flow (sMBF, rMBF) were quantified using the dual sequence technique. Myocardial perfusion reserve was calculated as sMBF/rMBF. Unpaired t-tests were used to test differences between the groups. RESULTS: The median time interval between COVID-19 infection and CMR was 5.6 (IQR: 4-8) months. No patients with the COVID-19 infection required hospitalization. Symptoms including chest pain, shortness of breath, syncope, and palpitations were more commonly present in the group with prior COVID-19 infection than in the control group (57% vs 7%, P < 0.001). No significant differences in rMBF (1.08 ± 0.27 mL/g/min vs 0.97 ± 0.29 mL/g/min, P = 0.16), sMBF (3.08 ± 0.79 mL/g/min vs 3.06 ± 0.89 mL/g/min, P = 0.91), or myocardial perfusion reserve (2.95 ± 0.90 vs 3.39 ± 1.25, P = 0.13) were observed between the groups. CONCLUSIONS: This study suggests that there are no significant abnormalities in rest or stress myocardial perfusion, and thus microvascular function, in individuals after mild COVID-19 infection.

SCMR expert consensus statement for cardiovascular magnetic resonance of patients with a cardiac implantable electronic device.

Cardiovascular magnetic resonance (CMR) is a proven imaging modality for informing diagnosis and prognosis, guiding therapeutic decisions, and risk stratifying surgical intervention. Patients with a cardiac implantable electronic device (CIED) would be expected to derive particular benefit from CMR given high prevalence of cardiomyopathy and arrhythmia. While several guidelines have been published over the last 16 years, it is important to recognize that both the CIED and CMR technologies, as well as our knowledge in MR safety, have evolved rapidly during that period. Given increasing utilization of CIED over the past decades, there is an unmet need to establish a consensus statement that integrates latest evidence concerning MR safety and CIED and CMR technologies. While experienced centers currently perform CMR in CIED patients, broad availability of CMR in this population is lacking, partially due to limited availability of resources for programming devices and appropriate monitoring, but also related to knowledge gaps regarding the risk-benefit ratio of CMR in this growing population. To address the knowledge gaps, this SCMR Expert Consensus Statement integrates consensus guidelines, primary data, and opinions from experts across disparate fields towards the shared goal of informing evidenced-based decision-making regarding the risk-benefit ratio of CMR for patients with CIEDs.

Cardiac Magnetic Resonance, Electromechanical Activation, Kidney Function, and Natriuretic Peptides in Cardiac Resynchronization Therapy Upgrades.

As the mechanism for worse prognosis after cardiac resynchronization therapy (CRT) upgrades in heart failure patients with RVP dependence (RVP-HF) has clinical implications for patient selection and CRT implementation approaches, this study's objective was to evaluate prognostic implications of cardiac magnetic resonance (CMR) findings and clinical factors in 102 HF patients (23.5% female, median age 66.5 years old, median follow-up 4.8 years) with and without RVP dependence undergoing upgrade and de novo CRT implants. Compared with other CRT groups, RVP-HF patients had decreased survival (p = 0.02), more anterior late-activated LV pacing sites (p = 0.002) by CMR, more atrial fibrillation (p = 0.0006), and higher creatinine (0.002). CMR activation timing at the LV pacing site predicted post-CRT LV functional improvement (p < 0.05), and mechanical activation onset < 34 ms by CMR at the LVP site was associated with decreased post-CRT survival in a model with higher pre-CRT creatinine and B-type natriuretic peptide (AUC 0.89; p < 0.0001); however, only the higher pre-CRT creatinine partially mediated (37%) the decreased survival in RVP-HF patients. In conclusion, RVP-HF had a distinct CMR phenotype, which has important implications for the selection of LV pacing sites in CRT upgrades, and only chronic kidney disease mediated the decreased survival after CRT in RVP-HF.

Impact of a Center of Excellence in Confirming or Excluding a Diagnosis of Hypertrophic Cardiomyopathy.

Tertiary hospitals with expertise in hypertrophic cardiomyopathy (HCM) are assuming a greater role in confirming and correcting HCM diagnoses at referring centers. The objectives were to establish the frequency of alternate diagnoses from referring centers and identify predictors of accuracy of an HCM diagnosis from the referring centers. Imaging findings from echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging (CMR) in 210 patients referred to an HCM Center of Excellence between September 2020 and October 2022 were reviewed. Clinical and imaging characteristics from pre-referral studies were used to construct a model for predictors of ruling out HCM or confirming the diagnosis using machine learning methods (least absolute shrinkage and selection operator logistic regression). Alternative diagnoses were found in 38 of the 210 patients (18.1%) (median age 60 years, 50% female). A total of 17 of the 38 patients (44.7%) underwent a new CMR after their initial visit, and 14 of 38 patients (36.8%) underwent review of a previous CMR. Increased left ventricular end-diastolic volume, indexed, greater septal thickness measurements, greater left atrial size, asymmetric hypertrophy on echocardiography, and the presence of an implantable cardioverter-defibrillator were associated with higher odds ratios for confirming a diagnosis of HCM, whereas increasing age and the presence of diabetes were more predictive of rejecting a diagnosis of HCM (area under the curve 0.902, p <0.0001). In conclusion, >1 in 6 patients with presumed HCM were found to have an alternate diagnosis after review at an HCM Center of Excellence, and both clinical findings and imaging parameters predicted an alternate diagnosis.

Cardiac Remodeling in Subclinical Hypertrophic Cardiomyopathy: The VANISH Randomized Clinical Trial.

Importance: Valsartan has shown promise in attenuating cardiac remodeling in patients with early-stage sarcomeric hypertrophic cardiomyopathy (HCM). Genetic testing can identify individuals at risk of HCM in a subclinical stage who could benefit from therapies that prevent disease progression. Objective: To explore the potential for valsartan to modify disease development, and to characterize short-term phenotypic progression in subclinical HCM. Design, Setting, and Participants: The multicenter, double-blind, placebo-controlled Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) randomized clinical trial was conducted from April 2014 to July 2019 at 17 sites in 4 countries (Brazil, Canada, Denmark, and the US), with 2 years of follow-up. The prespecified exploratory VANISH cohort studied here included sarcomere variant carriers with subclinical HCM and early phenotypic manifestations (reduced E' velocity, electrocardiographic abnormalities, or an increased left ventricular [LV] wall thickness [LVWT] to cavity diameter ratio) but no LV hypertrophy (LVH). Data were analyzed between March and December 2022. Interventions: Treatment with placebo or valsartan (80 mg/d for children weighing <35 kg, 160 mg/d for children weighing ≥35 kg, or 320 mg/d for adults aged ≥18 years). Main Outcomes and Measures: The primary outcome was a composite z score incorporating changes in 9 parameters of cardiac remodeling (LV cavity volume, LVWT, and LV mass; left atrial [LA] volume; E' velocity and S' velocity; and serum troponin and N-terminal prohormone of brain natriuretic peptide levels). Results: This study included 34 participants, with a mean (SD) age of 16 (5) years (all were White). A total of 18 participants (8 female [44%] and 10 male [56%]) were randomized to valsartan and 16 (9 female [56%] and 7 male [44%]) were randomized to placebo. No statistically significant effects of valsartan on cardiac remodeling were detected (mean change in composite z score compared with placebo: -0.01 [95% CI, -0.29 to 0.26]; P = .92). Overall, 2-year phenotypic progression was modest, with only a mild increase in LA volume detected (increased by 3.5 mL/m2 [95% CI, 1.4-6.0 mL/m2]; P = .002). Nine participants (26%) had increased LVWT, including 6 (18%) who developed clinically overt HCM. Baseline LA volume index (LAVI; 35 vs 28 mL/m2; P = .01) and average interventricular septum thickness (8.5 vs 7.0 mm; P = .009) were higher in participants who developed HCM. Conclusions and Relevance: In this exploratory cohort, valsartan was not proven to slow progression of subclinical HCM. Minimal changes in markers of cardiac remodeling were observed, although nearly one-fifth of patients developed clinically overt HCM. Transition to disease was associated with greater baseline interventricular septum thickness and LAVI. These findings highlight the importance of following sarcomere variant carriers longitudinally and the critical need to improve understanding of factors that drive disease penetrance and progression. Trial Registration: ClinicalTrials.gov Identifier: NCT01912534.

Preservation of Circumferential and Radial Left Ventricular Function as a Mitigating Mechanism for Impaired Longitudinal Strain in Early Cardiac Amyloidosis.

BACKGROUND: In patients with cardiac amyloidosis (CA), left ventricular ejection fraction (LVEF) is frequently preserved, despite commonly reduced global longitudinal strain (GLS). We hypothesized that nonlongitudinal contraction may initially serve as a mitigating mechanism to maintain cardiac output and studied the relationship between global circumferential (GCS) and radial (GRS) strain with LVEF and extracellular volume (ECV), a marker of amyloid burden. METHODS: Patients with CA who underwent cardiac magnetic resonance (CMR; n = 140, 70.7 ± 11.5 years, 66% male) or echocardiography (n = 67, 71 ± 13 years, 66% male) and normal controls (CMR, n = 20; echocardiography, n = 45) were retrospectively identified, and GCS, GLS, and GRS were quantified using feature-tracking CMR or speckle-tracking echocardiography and compared between CA patients with preserved and reduced LVEF (CAHFpEF, CAHFrEF) and controls. The prevalence of impaired strain (magnitudes <2.5th percentile of the controls) was compared between CAHFpEF and CAHFrEF and between ECV quartiles. RESULTS: While echocardiography-derived GLS was impaired in both CAHFpEF (-13.4% ± 3.1%, P < .003) and CAHFrEF (-9.1% ± 3.2%, P < .003), compared with controls (-20.8% ± 2.4%), GCS was more impaired in CAHFrEF compared with both controls (-15.6% ± 5.0% vs -32.3% ± 3.3%, P < .003) and CAHFpEF (-30.4% ± 5.7%, P < .003) and did not differ between CAHFpEF and controls (P = .24). The prevalence of abnormal CMR-derived GCS (P < .0001) and GRS (P < .0001) but not GLS (P = .054) varied significantly across ECV quartiles. CONCLUSIONS: Among CA patients with preserved LVEF, preserved GCS and GRS, despite near-universally impaired GLS, may be explained by an initial predominantly subendocardial involvement, where mostly longitudinal fibers are located. If confirmed in future studies, these findings may facilitate identification of patients with early stages of CA, when treatments may be most effective.

2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease." METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease." METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Sex-Specific Stress Perfusion Cardiac Magnetic Resonance Imaging in Suspected Ischemic Heart Disease: Insights From SPINS Retrospective Registry.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of mortality in women, but current noninvasive cardiac imaging techniques have sex-specific limitations. OBJECTIVES: In this study, the authors sought to investigate the effect of sex on the prognostic utility and downstream invasive revascularization and costs of stress perfusion cardiac magnetic resonance (CMR) for suspected CVD. METHODS: Sex-specific prognostic performance was evaluated in a 2,349-patient multicenter SPINS (Stress CMR Perfusion Imaging in the United States [SPINS] Study) Registry. The primary outcome measure was a composite of cardiovascular death and nonfatal myocardial infarction; secondary outcomes were hospitalization for unstable angina or heart failure, and late unplanned coronary artery bypass grafting. RESULTS: SPINS included 1,104 women (47% of cohort); women had higher prevalence of chest pain (62% vs 50%; P < 0.0001) but lower use of medical therapies. At the 5.4-year median follow-up, women with normal stress CMR had a low annualized rate of primary composite outcome similar to men (0.54%/y vs 0.75%/y, respectively; P = NS). In contrast, women with abnormal CMR were at higher risk for both primary (3.74%/y vs 0.54%/y; P < 0.0001) and secondary (9.8%/y vs 1.6%/y; P < 0.0001) outcomes compared with women with normal CMR. Abnormal stress CMR was an independent predictor for the primary (HR: 2.64 [95% CI: 1.20-5.90]; P = 0.02) and secondary (HR: 2.09 [95% CI: 1.43-3.08]; P < 0.0001) outcome measures. There was no effect modification for sex. Women had lower rates of invasive coronary angiography (3.6% vs 7.3%; P = 0.0001) and downstream costs ($114 vs $171; P = 0.001) at 90 days following CMR. There was no effect of sex on diagnostic image quality. CONCLUSIONS: Stress CMR demonstrated excellent prognostic performance with lower rates of invasive coronary angiography referral in women. Stress CMR should be considered as a first-line noninvasive imaging tool for the evaluation of women. (Stress CMR Perfusion Imaging in the United States [SPINS] Study [SPINS]; NCT03192891).

Qualitative and Quantitative Stress Perfusion Cardiac Magnetic Resonance in Clinical Practice: A Comprehensive Review.

Stress cardiovascular magnetic resonance (CMR) imaging is a well-validated non-invasive stress test to diagnose significant coronary artery disease (CAD), with higher diagnostic accuracy than other common functional imaging modalities. One-stop assessment of myocardial ischemia, cardiac function, and myocardial viability qualitatively and quantitatively has been proven to be a cost-effective method in clinical practice for CAD evaluation. Beyond diagnosis, stress CMR also provides prognostic information and guides coronary revascularisation. In addition to CAD, there is a large body of literature demonstrating CMR's diagnostic performance and prognostic value in other common cardiovascular diseases (CVDs), especially coronary microvascular dysfunction (CMD). This review focuses on the clinical applications of stress CMR, including stress CMR scanning methods, practical interpretation of stress CMR images, and clinical utility of stress CMR in a setting of CVDs with possible myocardial ischemia.

Myocardial Injury on CMR in Patients With COVID-19 and Suspected Cardiac Involvement.

BACKGROUND: Myocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood. OBJECTIVES: The purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR). METHODS: This retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction-confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR. RESULTS: In this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic: 13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95% CI: 1.17-3.40, P = 0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95% CI: 1.12-3.23; P = 0.02), natriuretic peptide elevation (OR: 2.99; 95% CI: 1.60-5.58; P = 0.0006), and troponin elevation (OR: 4.21; 95% CI: 2.41-7.36; P < 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95% CI: 1.04-9.49; P = 0.04), abnormal ECG (OR: 4.06; 95% CI: 1.10-14.92; P = 0.04), known coronary disease (OR: 33.30; 95% CI: 4.04-274.53; P = 0.001), hospitalization (OR: 4.98; 95% CI: 1.55-16.05; P = 0.007), natriuretic peptide elevation (OR: 4.19; 95% CI: 1.30-13.51; P = 0.02), and troponin elevation (OR: 25.27; 95% CI: 5.55-115.03; P < 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95% CI: 1.76-14.05; P = 0.003). CONCLUSIONS: In this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present.

Prognostic Value of RV Abnormalities on CMR in Patients With Known or Suspected Cardiac Sarcoidosis.

BACKGROUND: Left ventricular abnormalities in cardiac sarcoidosis (CS) are associated with adverse cardiovascular events, whereas the prognostic value of right ventricular (RV) involvement found on cardiac magnetic resonance is unclear. OBJECTIVES: This study aimed to systematically assess the prognostic value of right ventricular ejection fraction (RVEF) and RV late gadolinium enhancement (LGE) in known or suspected CS. METHODS: This study was prospectively registered in PROSPERO (CRD42022302579). PubMed, Embase, and Web of Science were searched to identify studies that evaluated the association between RVEF or RV LGE on clinical outcomes in CS. A composite endpoint of all-cause death, cardiovascular events, or sudden cardiac death (SCD) was used. A meta-analysis was performed to determine the pooled risk ratio (RR) for these adverse events. The calculated sensitivity, specificity, and area under the curve with 95% CIs were weighted and summarized. RESULTS: Eight studies including a total of 899 patients with a mean follow-up duration of 3.2 ± 0.7 years were included. The pooled RR of RV systolic dysfunction was 3.1 (95% CI: 1.7-5.5; P < 0.01) for composite events and 3.0 (95% CI: 1.3-7.0; P < 0.01) for SCD events. In addition, CS patients with RV LGE had a significant risk for composite events (RR: 4.8 [95% CI: 2.4-9.6]; P < 0.01) and a higher risk for SCD (RR: 9.5 [95% CI: 4.4-20.5]; P < 0.01) than patients without RV LGE. Furthermore, the pooled area under the curve, sensitivity, and specificity of RV LGE for identifying patients with CS who were at highest SCD risk were 0.8 (95% CI: 0.8-0.9), 69% (95% CI: 50%-84%), and 90% (95% CI: 70%-97%), respectively. CONCLUSIONS: In patients with known or suspected CS, RVEF and RV LGE were both associated with adverse events. Furthermore, RV LGE shows good discrimination in identifying CS patients at high risk of SCD.

Non-invasive diagnosis of transthyretin cardiac amyloidosis utilizing typical late gadolinium enhancement pattern on cardiac magnetic resonance and light chains.

AIMS: While cardiac magnetic resonance (CMR) is often obtained early in the evaluation of suspected cardiac amyloidosis (CA), it currently cannot be utilized to differentiate immunoglobulin (AL) and transthyretin (ATTR) CA. We aimed to determine whether a novel CMR and light-chain biomarker-based algorithm could accurately diagnose ATTR-CA. METHODS AND RESULTS: Patients with confirmed AL or ATTR-CA with typical late gadolinium enhancement (LGE) and Look-Locker pattern for CA on CMR were retrospectively identified at three academic medical centres. Comprehensive light-chain analysis including free light chains, serum, and urine electrophoresis/immunofixation was performed. The diagnostic accuracy of the typical CMR pattern for CA in combination with negative light chains for the diagnosis of ATTR-CA was determined both in the entire cohort and in the subset of patients with invasive tissue biopsy as the gold standard. A total of 147 patients (age 70 ± 11, 76% male, 51% black) were identified: 89 ATTR-CA and 58 AL-CA. Light-chain biomarkers were abnormal in 81 (55%) patients. Within the entire cohort, the sensitivity and specificity of a typical LGE and Look-Locker CMR pattern and negative light chains for ATTR-CA was 73 and 98%, respectively. Within the subset with biopsy-confirmed subtype, the CMR and light-chain algorithm were 69% sensitive and 98% specific. CONCLUSION: The combination of a typical LGE and Look-Locker pattern on CMR with negative light chains is highly specific for ATTR-CA. The successful non-invasive diagnosis of ATTR-CA using CMR has the potential to reduce diagnostic and therapeutic delays and healthcare costs for many patients.