Prognostic Value of Computed Tomography–Derived Extracellular Volume in TAVR Patients With Low-Flow Low-Gradient Aortic Stenosis

ObjectivesThe association between extracellular volume (ECV) measured by computed tomography angiography (CTA) and clinical outcomes was evaluated in low-flow low-gradient (LFLG) aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR).BackgroundPatients with LFLG AS comprise a high-risk group with respect to clinical outcomes. Although ECV, a marker of myocardial fibrosis, is traditionally measured with cardiac magnetic resonance, it can also be measured using cardiac CTA. The authors hypothesized that in LFLG AS, increased ECV may be associated with adverse clinical outcomes.MethodsIn 150 LFLG patients with AS who underwent TAVR, ECV was quantified using pre-TAVR CTA. Echocardiographic and clinical information including all-cause death and heart failure rehospitalization (HFH) was obtained from electronic medical records. A Cox proportional hazards model was used to evaluate the association between ECV and death+HFH.ResultsDuring a median follow-up of 13.9 months (range 0.07 to 28.9 months), there were 31 death+HFH events (21%). Patients who experienced death+HFH had a greater median Society of Thoracic Surgery score (9.9 vs. 4.7; p < 0.01), lower left ventricular ejection fraction (42.3 ± 20.2% vs. 52.7 ± 17.2%; p < 0.01), lower mean transvalvular gradient (24.9 ± 8.9 mm Hg vs. 28.1 ± 7.3 mm Hg; p = 0.04) and increased mean ECV (35.5 ± 9.6% vs. 29.9 ± 8.2%; p < 0.01) compared with patients who did not experience death+HFH. In a multivariable Cox proportional hazards model, increase in ECV was associated with increase in death+HFH, (hazard ratio per 1% increase: 1.04, 95% confidence interval: 1.01 to 1.09; p < 0.01).ConclusionsIn patients with LFLG AS, CTA measured increase in ECV is associated with increased risk of adverse clinical outcomes post-TAVR and may thus serve as a useful noninvasive marker for prognostication.     

Pittsburgh B Compound Positron Emission Tomography in Patients With AL Cardiac Amyloidosis

BackgroundIt remains unknown whether the noninvasive evaluation of the degree of amyloid deposition in the myocardium can predict the prognosis of patients with light chain (AL) cardiac amyloidosis.ObjectivesThe purpose of this study was to demonstrate that ¹¹C-Pittsburgh B compound positron emission tomography (¹¹C-PiB PET) is useful for prognostication of AL cardiac amyloidosis by noninvasively imaging the myocardial AL amyloid deposition.MethodsThis study consecutively enrolled 41 chemotherapy-naïve AL cardiac amyloidosis patients. The amyloid deposit was quantitatively assessed with amyloid P immunohistochemistry in endomyocardial biopsy specimens and was compared with the degree of myocardial ¹¹C-PiB uptake on PET. The primary endpoint was a composite of all-cause death, heart transplantation, and acute decompensated heart failure.ResultsThe degree of myocardial ¹¹C-PiB PET uptake was significantly higher in the cardiac amyloidosis patients compared with normal subjects and correlated well with the degree of amyloid deposit on histology (R² = 0.343, p < 0.001). During follow-up (median: 423 days, interquartile range: 93 to 1,222 days), 24 patients experienced the primary endpoint. When the cardiac amyloidosis patients were divided into tertiles by the degree of myocardial ¹¹C-PiB PET uptake, patients with the highest PiB uptake experienced the worst clinical event-free survival (log-rank p = 0.014). The degree of myocardial PiB PET uptake was a significant predictor of clinical outcome on multivariate Cox regression analysis (adjusted hazard ratio: 1.185; 95% confidence interval: 1.054 to 1.332; p = 0.005).ConclusionsThese proof-of-concept results show that noninvasive evaluation of myocardial amyloid load by ¹¹C-PiB PET reflects the degree of amyloid deposit and is an independent predictor of clinical outcome in AL cardiac amyloidosis patients.     

Exercise Pulmonary Hypertension Predicts Clinical Outcomes in Patients With Dyspnea on Effort

BackgroundAbnormal pulmonary arterial pressure (PAP) responses to exercise have been described in select individuals; however, clinical and prognostic implications of exercise pulmonary hypertension (exPH) among broader samples remains unclear.ObjectivesThis study sought to investigate the association of exPH with clinical determinants and outcomes.MethodsThe authors studied individuals with chronic exertional dyspnea and preserved ejection fraction who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring. Exercise pulmonary hypertension was ascertained using minute-by-minute PAP and cardiac output (CO) measurements to calculate a PAP/CO slope, and exPH defined as a PAP/CO slope >3 mm Hg/l/min. The primary outcome was cardiovascular (CV) hospitalization or all-cause mortality.ResultsAmong 714 individuals (age 57 years, 59% women), 296 (41%) had abnormal PAP/CO slopes. Over a mean follow-up of 3.7 ± 2.9 years, there were 208 CV or death events. Individuals with abnormal PAP/CO slope had a 2-fold increased hazard of future CV or death event (multivariable-adjusted hazard ratio: 2.03; 95% confidence interval: 1.48 to 2.78; p < 0.001). The association of abnormal PAP/CO slope with outcomes remained significant after excluding rest PH (n = 146, hazard ratio: 1.75; 95% confidence interval: 1.21 to 2.54; p = 0.003). Both pre- and post-capillary contributions to exPH independently predicted adverse events (p < 0.001 for both).ConclusionsExercise pulmonary hypertension is independently associated with CV event-free survival among individuals undergoing evaluation of chronic dyspnea. These findings suggest incremental value of exercise hemodynamic assessment to resting measurements alone in characterizing the burden of PH in individuals with dyspnea. Whether PH and PH subtypes unmasked by exercise can be used to guide targeted therapeutic interventions requires further investigation.     

T1 Mapping and Extracellular Volume Fraction in Dilated Cardiomyopathy: A Prognosis Study

ObjectivesThe aim of this study is to examine the prognostic value of T1 mapping and the extracellular volume (ECV) fraction in patients with dilated cardiomyopathy (DCM).BackgroundPatients with DCM with functional left ventricular remodeling have poorer prognoses. Noninvasive assessment of myocardial fibrosis using T1 mapping and the ECV fraction may improve risk stratification of patients with DCM; however, this has not yet been systematically evaluated.MethodsA total of 659 consecutive patients with DCM (498 men; 45 ± 15 years) who underwent cardiac magnetic resonance with T1 mapping and late gadolinium enhancement (LGE) imaging with a 1.5-T magnetic resonance scanner were enrolled in this study. Primary endpoints were cardiac-related death and heart transplantation. Secondary endpoints were hospitalization for heart failure, ventricular arrhythmias, and implantable cardioverter-defibrillator or cardiac resynchronization therapy implantation. Survival estimates were calculated by Kaplan-Meier curves with the log-rank test.ResultsDuring a mean follow-up of 66.3 ± 20.9 months, 122 and 205 patients with DCM reached the primary and secondary endpoints, respectively. The presence of LGE had an association with both of the primary and secondary endpoints observed in the patients with DCM (both P < 0.001). The maximum native T1 (HR: 1.04; 95% CI: 1.02-1.09) and maximum ECV fraction (HR: 1.14; 95% CI: 1.08-1.21) had associations with the primary endpoints in the patients with positive LGE (both P < 0.001), whereas the mean native T1 (HR: 1.13; 95% CI: 1.10-1.36) and mean ECV fraction (HR: 1.32; 95% CI: 1.12-1.53) had the best associations in the patients with negative LGE (all P < 0.001).ConclusionsT1 mapping and the ECV fraction had prognostic value in patients with DCM and were particularly important in patients with DCM without LGE. Using a combination of T1 mapping, ECV fraction, and LGE provided optimal risk stratification for patients with DCM.     

Prognostic Value of Stress Dynamic Computed Tomography Perfusion With Computed Tomography Delayed Enhancement

ObjectivesThis study sought to evaluate the prognostic value of stress dynamic computed tomography (CT) perfusion (CTP) with CT delayed enhancement (CTDE) in patients with suspected or known coronary artery disease (CAD) and in subgroups of patients with stent, heavy calcification, or stenosis.BackgroundThe prognostic value of stress dynamic CTP with CTDE is unknown.MethodsParticipants were 540 patients with suspected or known CAD. Major adverse cardiac event(s) (MACE) consisted of cardiac death, nonfatal myocardial infarction, unstable angina, or hospitalization for congestive heart failure. Ischemic score was calculated by scoring the reduction of normalized myocardial blood flow in 16 segments excluding areas of myocardial scarring. Ischemic perfusion defect (IPD) was defined as Ischemic score ≥4. Scar score was also calculated by scoring the transmural extent of scarring in each segment on CTDE.ResultsDuring a median follow-up of 2.9 years, 43 MACEs occurred. By adding IPD to obstructive CAD (≥50% stenosis) on coronary CT angiography, the concordance index for predicting MACEs increased from 0.73 to 0.82 in patients with suspected CAD (p = 0.028) and from 0.61 to 0.73 in patients with known CAD (p = 0.004). IPD and scar score of ≥4 were independent predictors when adjusted for each other in patients with suspected (adjusted hazard ratios: 7.5 [p < 0.001] and 3.0 [p = 0.034], respectively) or known CAD (adjusted hazard ratios: 4.4 [p = 0.001] and 3.2 [p = 0.024], respectively). Patients with IPD had a higher annualized event rate than those without IPD in subgroups of those with stent (11.5% vs. 2.6%; p < 0.001), heavy calcification (13.3% vs. 3.1%; p < 0.001), 50% to 69% stenosis (8.8% vs. 1.0%; p < 0.001), or ≥70% stenosis (12.4% vs. 3.6%; p < 0.001).ConclusionsStress dynamic CTP with CTDE had incremental prognostic value over CT angiography in each group with suspected or known CAD and was prognostically useful in subgroups of patients with stent, heavy calcification, or obstructive CAD. IPD and myocardial scarring may play complementary roles in prognostic stratification.     

Dynamic Stress Computed Tomography Perfusion With a Whole-Heart Coverage Scanner in Addition to Coronary Computed Tomography Angiography and Fractional Flow Reserve Computed Tomography Derived

ObjectivesThe aims of the study were to test the diagnostic accuracy of integrated evaluation of dynamic myocardial computed tomography perfusion (CTP) on top of coronary computed tomography angiography (cCTA) plus fractional flow reserve computed tomography derived (FFR_CT) by using a whole-heart coverage computed tomography (CT) scanner as compared with clinically indicated invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR).BackgroundRecently, new techniques such as dynamic stress computed tomography perfusion (stress-CTP) emerged as potential strategies to combine anatomical and functional evaluation in a one-shot scan. However, previous experiences with this technique were associated with high radiation exposure.MethodsEighty-five consecutive symptomatic patients scheduled for ICA were prospectively enrolled. All patients underwent rest cCTA followed by stress dynamic CTP with a whole-heart coverage CT scanner (Revolution CT, GE Healthcare, Milwaukee, Wisconsin). FFR_CT was also measured by using the rest cCTA dataset. The diagnostic accuracy to detect functionally significant coronary artery disease (CAD) in a vessel-based model of cCTA alone, cCTA+FFR_CT, cCTA+CTP, or cCTA+FFR_CT+CTP were assessed and compared by using ICA and invasive FFR as reference. The overall effective dose of dynamic CTP was also measured.ResultsThe prevalence of obstructive CAD and functionally significant CAD was 77% and 57%, respectively. The sensitivity and specificity of cCTA alone, cCTA+FFR_CT, and cCTA+CTP were 83% and 66%, 86% and 75%, and 73% and 86%, respectively. Both the addition of FFR_CT and CTP improves the area under the curve (AUC: 0.876 and 0.878, respectively) as compared with cCTA alone (0.826; p < 0.05). The sequential strategy of cCTA+FFR_CT+CTP showed the highest AUC (0.919; p < 0.05) as compared with all other strategies. The mean effective radiation dose (ED) for cCTA and stress CTP was 2.8 ± 1.2 mSv and 5.3 ± 0.7 mSv, respectively.ConclusionsThe addition of dynamic stress CTP on top of cCTA and FFR_CT provides additional diagnostic accuracy with acceptable radiation exposure.     

Native T1 Mapping,Extracellular Volume Mapping,and Late Gadolinium Enhancement in Cardiac Amyloidosis: A Meta-Analysis

ObjectivesThis study aimed to compare the diagnostic and prognostic performance of native T1 mapping (T1), extracellular volume (ECV) mapping, and late gadolinium enhancement (LGE) imaging for evaluating cardiac amyloidosis (CA).BackgroundCA is a progressive infiltrative process in the extracellular space that is often underdiagnosed and holds a poor prognosis. Cardiac magnetic resonance (CMR) offers novel techniques for detecting and quantifying the disease burden of CA.MethodsWe searched PubMed for published studies using native T1, ECV, or LGE to diagnose and prognosticate CA. A total of 18 diagnostic (n = 2,015) and 13 prognostic studies (n = 1,483) were included for analysis. Pooled sensitivities, specificities, diagnostic odds ratios (DORs) of all diagnostic tests were assessed by bivariate analysis. Pooled hazard ratios (HRs) for mortality for the 3 techniques were determined.ResultsBivariate comparison showed that ECV (DOR: 84.6; 95% confidence interval [CI]: 30.3 to 236.2) had a significantly higher DOR for CA than LGE (DOR: 20.1; 95% CI: 9.1 to 44.1; p = 0.03 vs. ECV). There was no significant difference between LGE and native T1 for sensitivity, specificity, and DOR. HR was significantly higher for ECV (HR: 4.27; 95% CI: 2.87 to 6.37) compared with LGE (HR: 2.60; 95% CI: 1.90 to 3.56; p = 0.03 vs. ECV) and native T1 (HR: 2.04; 95% CI: 1.24 to 3.37; p = 0.01 vs. ECV).ConclusionsECV demonstrates a higher diagnostic OR for assessing cardiac amyloid than LGE and a higher HR for adverse events compared with LGE and native T1. In addition, native T1 showed similar sensitivity and specificity as ECV and LGE without requiring contrast material. Although limited by study heterogeneity, this meta-analysis suggests that ECV provides high diagnostic and prognostic utility for the assessment of cardiac amyloidosis.     

Prognostic Implications of Left Atrial Stiffness Index in Heart Failure Patients With Preserved Ejection Fraction

BackgroundThe left atrium (LA) plays an important role in the pathophysiology and disease progression of heart failure with preserved ejection fraction (HFpEF).ObjectivesThis study sought to assess the prognostic potential of LA stiffness index in patients who have HFpEF.MethodsThis study retrospectively screened patients with elevated left ventricular end-diastolic pressure (≥16 mm Hg) and preserved ejection fraction (≥50%) between January 1, 2004, and December 31, 2019. All patients underwent left heart catheterization to measure left ventricular end-diastolic pressure. Among these, 307 patients who had suitable image quality for left peak atrial longitudinal strain (PALS) measurement were analyzed. The study population was classified into low LA stiffness (n = 178, early diastolic transmitral inflow velocity/mitral annulus early diastolic velocity [E/e′]/PALS ≤0.26) and high LA stiffness (n = 129, E/e′/PALS >0.26) according to the best LA stiffness index (E/e′/PALS) cutoff value. The primary outcome was a composite of mortality or hospitalization caused by heart failure during follow-up.ResultsLA stiffness index showed good correlations with E/e′ (r = 0.737; P < 0.001), LA volume index (r = 0.529; P < 0.001), right ventricular systolic pressure (r = 0.404; P < 0.001), and log N-terminal pro–B-type natriuretic peptide (r = 0.540; P < 0.001). LA stiffness index demonstrated better predictive performance than echocardiographic diastolic parameters did (P < 0.001). Patients with low LA stiffness had better clinical outcomes than those with high LA stiffness during a median follow-up of 6 years did (P < 0.001). In multivariable analysis, LA stiffness index was independently associated with increased risk of the composite endpoint of death or heart failure hospitalization (HR: 1.59 [95% CI: 1.01-2.51]; P = 0.044).ConclusionsIncreased LA stiffness was associated with increased risk for all-cause mortality and hospitalization caused by heart failure in patients who have HFpEF, and its prognostic role was more pronounced than that of indexes of left ventricular filling pressure.     

Unveiling Cardiac Amyloidosis,its Characteristics,and Outcomes Among Patients With MR Undergoing Transcatheter Edge-to-Edge MV Repair

BackgroundMitral regurgitation (MR) and cardiac amyloidosis (CA) both primarily affect older patients. Data on coexistence and prognostic implications of MR and CA are currently lacking.ObjectivesThis study sought to identify the prevalence, clinical characteristics, and outcomes of MR CA compared with lone MR.MethodsConsecutive patients undergoing transcatheter edge-to-edge repair (TEER) for MR at 2 sites were screened for concomitant CA using a multiparametric approach including core laboratory ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid bone scintigraphy and echocardiography and immunoglobulin light chain assessment. Transthyretin CA (ATTR) was diagnosed by ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (Perugini grade 1: early infiltration; grades 2/3: clinical CA) and the absence of monoclonal protein, and light chain (AL) CA via tissue biopsy. All-cause mortality and hospitalization for heart failure (HHF) served as the endpoints.ResultsA total of 120 patients (age 76.9 ± 8.1 years, 55.8% male) were recruited. Clinical CA was diagnosed in 14 patients (11.7%; 12 ATTR, 1 AL, and 1 combined ATTR/AL) and early amyloid infiltration in 9 patients (7.5%). Independent predictors of MR CA were increased posterior wall thickness and the presence of a left anterior fascicular block on electrocardiography. Procedural success and periprocedural complications of TEER were similar in MR CA and lone MR (P for all = NS). After a median of 1.7 years, 25.8% had experienced death and/or HHF. MR CA had worse outcomes compared with lone MR (HR: 2.2; 95% CI: 1.0-4.7; P = 0.034), driven by a 2.5-fold higher risk for HHF (HR: 2.5; 95% CI: 1.1-5.9), but comparable mortality (HR: 1.6; 95% CI: 0.4-6.1).ConclusionsDual pathology of MR CA is common in elderly patients with MR undergoing TEER and has worse postinterventional outcomes compared with lone MR.     

Diagnostic Accuracy of Cardiac Computed Tomography and 18-F Fluorodeoxyglucose Positron Emission Tomography in Cardiac Masses

ObjectivesThis study sought to assess the diagnostic accuracy of cardiac computed tomography (CT) and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) with positron emission tomography/computed tomography (PET/CT) in defining the nature of cardiac masses.BackgroundThe diagnostic accuracy of cardiac CT and ¹⁸F-FDG PET/CT in identifying the nature of cardiac masses has been analyzed to date only in small samples.MethodsOf 223 patients with echocardiographically diagnosed cardiac masses, a cohort of 60 cases who underwent cardiac CT and ¹⁸F-FDG PET/CT was selected. All masses had histological confirmation, except for a minority of thrombotic formations. For each mass, 8 morphological CT signs, standardized uptake value (SUV_max, SUV_mean), metabolic tumor volume, and total lesion glycolysis in ¹⁸F-FDG PET were used as diagnostic markers.ResultsIrregular tumor margins, pericardial effusion, invasion, solid nature, mass diameter, CT contrast uptake, and pre-contrast characteristics were strongly associated with the malignant nature of masses. The coexistence of at least 5 CT signs perfectly identified malignant masses, whereas the detection of 3 or 4 CT signs did not accurately discriminate the masses’ nature. The mean SUV_max, SUV_mean, metabolic tumor volume, and total lesion glycolysis values were significantly higher in malignant than in benign masses. The diagnostic accuracy of SUV, metabolic tumor volume, and total lesion glycolysis ¹⁸F-FDG PET/CT parameters was excellent in detecting malignant masses. Among patients with 3 or 4 pathological CT signs, the presence of at least 1 abnormal ¹⁸F-FDG PET/CT parameter significantly increased the identification of malignancies.ConclusionsCardiac CT is a powerful tool to diagnose cardiac masses as the number of abnormal signs was found to correlate with the lesions’ nature. Similarly, ¹⁸F-FDG PET/CT accurately identified malignant masses and contributed with additional valuable information in diagnostic uncertainties after cardiac CT. These imaging tools should be performed in specific clinical settings such as involvement of great vessels or for disease-staging purposes.     

Long-Term Prognosis of Patients With Coronary Microvascular Disease Using Stress Perfusion Cardiac Magnetic Resonance

ObjectivesThis study investigated the prognosis of coronary microvascular disease (CMD) as determined by stress perfusion cardiac magnetic resonance (CMR) in patients with ischemic symptoms but without significant coronary artery disease (CAD).BackgroundPatients with CMD have poorer prognosis with various cardiac diseases. The myocardial perfusion reserve index (MPRI) derived from noninvasive stress perfusion CMR has been established to diagnose microvascular angina with a threshold MPRI <1.4. The prognosis of CMD as determined by MPRI is unknown.MethodsChest pain patients without epicardial CAD or myocardial disease from January 2009 to December 2017 were retrospectively included from 3 imaging centers in Hong Kong (HK). Stress perfusion CMR examinations were performed using either adenosine or adenosine triphosphate. Adequate stress was assessed by achieving splenic switch-off sign. Measurement of MPRI was performed in all stress perfusion CMR scans. Patients were followed for major adverse cardiovascular events defined as all-cause death, acute coronary syndrome (ACS), epicardial CAD development, heart failure hospitalization and non-fatal stroke.ResultsA total of 218 patients were studied (mean age 59 ± 12 years; 49.5% male) and the average MPRI of that cohort was 1.56 ± 0.33. Females and a history of hyperlipidemia were predictors of lower MPRI. Major adverse cardiovascular events (MACE) occurred in 15.6% of patients during a median follow-up of 5.5 years (interquartile range: 4.6 to 6.8 years). The optimal cutoff value of MPRI in predicting MACE was found with a threshold MPRI ≤1.47. Patients with MPRI ≤1.47 had three-fold increased risk of MACE compared with those with MPRI >1.47 (hazard ratio [HR]: 3.14; 95% confidence interval [CI]: 1.58 to 6.25; p = 0.001). Multivariate Cox regression after adjusting for age and hypertension demonstrated that MPRI was an independent predictor of MACE (HR: 0.10; 95% CI: 0.03 to 0.34; p < 0.001).ConclusionsStress perfusion CMR-derived MPRI is an independent imaging marker that predicts MACE in patients with ischemic symptom and no overt CAD over the medium term.     

Pre-Treatment Myocardial 18FDG Uptake Predicts Response to Immunosuppression in Patients With Cardiac Sarcoidosis

ObjectivesThis study identified predictors of clinical (CR) and echocardiographic response (ER) following immunosuppressive therapy (IST) in patients with cardiac sarcoidosis (CS).BackgroundIST has been the cornerstone of treatment for patients with CS and active myocardial inflammation. However, there are little data to explain the variable response to IST in CS.MethodsData of 96 consecutive patients with CS from the Granulomatous Myocarditis Registry were analyzed. All patients underwent a ¹⁸fluorodeoxy glucose positron emission tomography−computed tomography (¹⁸FDG-PET-CT) before initiation of IST. Response was assessed after 4 to 6 months of therapy. CR was defined as an improvement in functional class (New York Heart Association functional class ≥I) and freedom from ventricular arrhythmias and heart failure hospitalizations. ER was defined as an improvement in left ventricular ejection fraction (LVEF) ≥10%. ER was assessed only in patients with a LVEF <50%. Complete responders had no residual myocardial FDG uptake and fulfilled both response criteria. Partial responders fulfilled only 1 response criteria or had residual FDG uptake. Nonresponders did not fulfill either CR or ER criteria. The uptake index (UI) was defined as the product of maximum standardized uptake value and the number of LV segments with abnormal uptake on ¹⁸FDG-PET-CT.ResultsAmong 91 patients included in the final analysis, 54.9%, 20.9%, and 24.2% of patients were classified as complete and partial responders and nonresponders, respectively. Cox regression analysis (all responders vs. nonresponders) identified the following as independent predictors of response following immunosuppression: LVEF >40% (hazard ratio: 1.61; 95% confidence interval: 1.06 to 7.69; p = 0.031) and myocardial UI >30 (hazard ratio: 1.28; 95% confidence interval: 1.05 to 6.12; p = 0.010). The final model had a good discriminative power (area under the curve [AUC]: 0.85) and predictive accuracy (sensitivity: 85.5%; specificity: 86.4%). Pre-treatment myocardial UI had a strong positive correlation with change in LVEF following immunosuppression.ConclusionsPre-treatment ¹⁸FDG myocardial uptake was a predictor of CR and ER response to immunosuppression in patients with CS.     

Reduction in CMR Derived Extracellular Volume With Patisiran Indicates Cardiac Amyloid Regression

ObjectivesThe purpose of this study was to determine the effect of patisiran on the cardiac amyloid load as measured by cardiac magnetic resonance and extracellular volume (ECV) mapping in cases of transthyretin cardiomyopathy (ATTR-CM).BackgroundAdministration of patisiran, a TTR-specific small interfering RNA (siRNA), has been shown to benefit neuropathy in patients with hereditary ATTR amyloidosis, but its effect on ATTR-CM remains uncertain.MethodsPatisiran was administered to 16 patients with hereditary ATTR-CM who underwent assessment protocols at the UK National Amyloidosis Centre. Twelve of those patients concomitantly received diflunisal as a “TTR-stabilizing” drug. Patients underwent serial monitoring using cardiac magnetic resonance, echocardiography, cardiac biomarkers, bone scintigraphy, and 6-min walk tests (6MWTs). Findings of amyloid types and extracellular volumes were compared with those of 16 patients who were retrospectively matched based on cardiac magnetic resonance results.ResultsPatisiran was well tolerated. Median serum TTR knockdown among treated patients was 86% (interquartile range [IQR]: 82% to 90%). A total of 82% of cases showed >80% knockdown. Patisiran therapy was typically associated with a reduction in ECV (adjusted mean difference between groups: ?6.2% [95% confidence interval [CI]: ?9.5% to ?3.0%]; p = 0.001) accompanied by a fall in N-terminal pro–B-type natriuretic peptide concentrations (adjusted mean difference between groups: ?1,342 ng/l [95% CI: ?2,364 to ?322]; p = 0.012); an increase in 6MWT distances (adjusted mean differences between groups: 169 m [95% CI: 57 to 2,80]; p = 0.004) after 12 months of therapy; and a median reduction in cardiac uptake by bone scintigraphy of 19.6% (IQR: 9.8% to 27.1%).ConclusionsReductions in ECV by cardiac magnetic resonance provided evidence for ATTR cardiac amyloid regression in a proportion of patients receiving patisiran.     

Tracking Multiorgan Treatment Response in Systemic AL-Amyloidosis With Cardiac Magnetic Resonance Derived Extracellular Volume Mapping

BackgroundSystemic light chain amyloidosis is a multisystem disorder that commonly involves the heart, liver, and spleen. Cardiac magnetic resonance with extracellular volume (ECV) mapping provides a surrogate measure of the myocardial, liver, and spleen amyloid burden.ObjectivesThe purpose of this study was to assess multiorgan response to treatment using ECV mapping, and assess the association between multiorgan treatment response and prognosis.MethodsThe authors identified 351 patients who underwent baseline serum amyloid-P-component (SAP) scintigraphy and cardiac magnetic resonance at diagnosis, of which 171 had follow-up imaging.ResultsAt diagnosis, ECV mapping demonstrated that 304 (87%) had cardiac involvement, 114 (33%) significant hepatic involvement, and 147 (42%) significant splenic involvement. Baseline myocardial and liver ECV independently predict mortality (myocardial HR: 1.03 [95% CI: 1.01-1.06]; P = 0.009; liver HR: 1.03; [95% CI: 1.01-1.05]; P = 0.001). Liver and spleen ECV correlated with amyloid load assessed by SAP scintigraphy (R = 0.751; P < 0.001; R = 0.765; P < 0.001, respectively). Serial measurements demonstrated ECV correctly identified changes in liver and spleen amyloid load derived from SAP scintigraphy in 85% and 82% of cases, respectively. At 6 months, more patients with a good hematologic response had liver (30%) and spleen (36%) ECV regression than myocardial regression (5%). By 12 months, more patients with a good response demonstrated myocardial regression (heart 32%, liver 30%, spleen 36%). Myocardial regression was associated with reduced median N-terminal pro-brain natriuretic peptide (P < 0.001), and liver regression with reduced median alkaline phosphatase (P = 0.001). Changes in myocardial and liver ECV, 6 months after initiating chemotherapy, independently predict mortality (myocardial HR: 1.11 [95% CI: 1.02-1.20]; P = 0.011; liver HR: 1.07 [95% CI: 1.01-1.13]; P = 0.014).ConclusionsMultiorgan ECV quantification accurately tracks treatment response and demonstrates different rates of organ regression, with the liver and spleen regressing more rapidly than the heart. Baseline myocardial and liver ECV and changes at 6 months independently predict mortality, even after adjusting for traditional predictors of prognosis.     

Extracellular Myocardial Volume in Patients With Aortic Stenosis

BackgroundMyocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis.ObjectivesThis study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes.MethodsPatients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery–based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters.ResultsFour-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p < 0.05 for all), the latter 2 associations being independent of all other clinical variables (p = 0.035 and p < 0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p = 0.009). Not only was ECV% associated with cardiovascular mortality (p = 0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% confidence interval [1.02 to 1.19]; p = 0.013).ConclusionsIn patients with severe aortic stenosis scheduled for aortic valve intervention, an increased ECV% is a measure of left ventricular decompensation and a powerful independent predictor of mortality.     

First-Phase Ejection Fraction Predicts Response to Cardiac Resynchronization Therapy and Adverse Outcomes

ObjectivesThe aim of this study was to examine the value of first-phase ejection fraction (EF1), to predict response to cardiac resynchronization therapy (CRT) and clinical outcomes after CRT.BackgroundCRT is an important treatment for patients with chronic heart failure. However, even in carefully selected cases, up to 40% of patients fail to respond. EF1, the ejection fraction up to the time of maximal ventricular contraction, is a novel sensitive echocardiographic measure of early systolic function and might relate to response to CRT.MethodsAn initial retrospective study was performed in 197 patients who underwent CRT between 2009 and 2018 and were followed to determine clinical outcomes at King’s Health Partners in London. A validation study (n = 100) was performed in patients undergoing CRT at Barts Heart Centre in London.ResultsVolumetric response rate (reduction in end-systolic volume ≥15%) was 92.3% and 12.1% for those with EF1 in the highest and lowest tertiles (P < 0.001). A cutoff value of 11.9% for EF1 had >85% sensitivity and specificity for prediction of response to CRT; on multivariate binary logistic regression analysis incorporating previously defined predictors, EF1 was the strongest predictor of response (odds ratio [OR]: 1.56 per 1% change in EF1; 95% CI: 1.37-1.78; P < 0.001). EF1 was also the strongest predictor of improvement in clinical composite score (OR: 1.11; 95% CI: 1.04-1.19; P = 0.001). Improvement in EF1 at 6 months after CRT implantation (6.5% ± 5.8% vs 1.8% ± 4.3% in responders vs nonresponders; P < 0.001) was the best predictor of heart failure rehospitalization and death after median follow-up period of 20.3 months (HR: 0.81; 95% CI: 0.73-0.90; P < 0.001). In the validation cohort, EF1 was a similarly 1strong predictor of response (OR: 1.45; 95% CI: 1.23-1.70; P < 0.001) as in the original cohort.ConclusionsEF1 is a promising marker to identify patients likely to respond to CRT.     

Myocardial Histopathology in Patients With Obstructive Hypertrophic Cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) is characterized by multiple pathological features including myocyte hypertrophy, myocyte disarray, and interstitial fibrosis.ObjectivesThis study sought to correlate myocardial histopathology with clinical characteristics of patients with obstructive HCM and post-operative outcomes following septal myectomy.MethodsThe authors reviewed the pathological findings of the myocardial specimens from 1,836 patients with obstructive HCM who underwent septal myectomy from 2000 to 2016. Myocyte hypertrophy, myocyte disarray, interstitial fibrosis, and endocardial thickening were graded and analyzed.ResultsThe median age at operation was 54.2 years (43.5 to 64.3 years), and 1,067 (58.1%) were men. A weak negative correlation between myocyte disarray and age at surgery was identified (ρ = ?0.22; p < 0.001). Myocyte hypertrophy (p < 0.001), myocyte disarray (p < 0.001), and interstitial fibrosis (p < 0.001) were positively associated with implantable cardioverter-defibrillator implantation. Interstitial fibrosis (p < 0.001) and endocardial thickening (p < 0.001) were associated with atrial fibrillation pre-operatively. In the Cox survival model, older age (p < 0.001), lower degree of myocyte hypertrophy (severe vs. mild hazard ratio: 0.41; 95% confidence interval: 0.19 to 0.86; p = 0.040), and lower degree of endocardial thickening (moderate vs. mild hazard ratio: 0.75; 95% confidence interval: 0.58 to 0.97; p = 0.019) were independently associated with worse post-myectomy survival. Among 256 patients who had genotype analysis, patients with pathogenic or likely pathogenic variants (n = 62) had a greater degree of myocyte disarray (42% vs. 15% vs. 20%; p = 0.022). Notably, 13 patients with pathogenic or likely pathogenic genetic variants of HCM had no myocyte disarray.ConclusionsHistopathology was associated with clinical manifestations including the age of disease onset and arrhythmias. Myocyte hypertrophy and endocardial thickening were negatively associated with post-myectomy mortality.     

Prognostic Value of Initial Left Ventricular Remodeling in Patients With Reperfused STEMI

ObjectivesThis study sought to establish the best definition of left ventricular adverse remodeling (LVAR) to predict outcomes and determine whether its assessment adds prognostic information to that obtained by early cardiac magnetic resonance (CMR).BackgroundLVAR, usually defined as an increase in left ventricular end-diastolic volume (LVEDV) is the main cause of heart failure after an ST-segment elevated myocardial infarction; however, the role of assessment of LVAR in predicting cardiovascular events remains controversial.MethodsPatients with ST-segment elevated myocardial infarction who received percutaneous coronary intervention within 6 h of symptom onset were included (n = 498). CMR was performed during hospitalization (6.2 ± 2.6 days) and after 6 months (6.1 ± 1.8 months). The optimal threshold values of the LVEDV increase and the LV ejection fraction decrease associated with the primary endpoint were ascertained. Primary outcome was a composite of cardiovascular mortality, hospitalization for heart failure, or ventricular arrhythmia.ResultsThe study was completed by 374 patients. Forty-nine patients presented the primary endpoint during follow-up (72.9 ± 42.8 months). Values that maximized the ability to identify patients with and without outcomes were a relative rise in LVEDV of 15% (hazard ratio [HR]: 2.1; p = 0.007) and a relative fall in LV ejection fraction of 3% (HR: 2.5; p = 0.001). However, the predictive model (using C-statistic analysis) failed to demonstrate that direct observation of LVAR at 6 months adds information to data from early CMR in predicting outcomes (C-statistic: 0.723 vs. 0.795).ConclusionsThe definition of LVAR that best predicts adverse cardiovascular events should consider both the increase in LVEDV and the reduction in LV ejection fraction. However, assessment of LVAR does not improve information provided by the early CMR.