Desmoplakin Cardiomyopathy, a Fibrotic and Inflammatory Form of Cardiomyopathy Distinct From Typical Dilated or Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Mutations in desmoplakin (DSP), the primary force transducer between cardiac desmosomes and intermediate filaments, cause an arrhythmogenic form of cardiomyopathy that has been variably associated with arrhythmogenic right ventricular cardiomyopathy. Clinical correlates of DSP cardiomyopathy have been limited to small case series. METHODS: Clinical and genetic data were collected on 107 patients with pathogenic DSP mutations and 81 patients with pathogenic plakophilin 2 (PKP2) mutations as a comparison cohort. A composite outcome of severe ventricular arrhythmia was assessed. RESULTS: DSP and PKP2 cohorts included similar proportions of probands (41% versus 42%) and patients with truncating mutations (98% versus 100%). Left ventricular (LV) predominant cardiomyopathy was exclusively present among patients with DSP (55% versus 0% for PKP2, P<0.001), whereas right ventricular cardiomyopathy was present in only 14% of patients with DSP versus 40% for PKP2 (P<0.001). Arrhythmogenic right ventricular cardiomyopathy diagnostic criteria had poor sensitivity for DSP cardiomyopathy. LV late gadolinium enhancement was present in a primarily subepicardial distribution in 40% of patients with DSP (23/57 with magnetic resonance images). LV late gadolinium enhancement occurred with normal LV systolic function in 35% (8/23) of patients with DSP. Episodes of acute myocardial injury (chest pain with troponin elevation and normal coronary angiography) occurred in 15% of patients with DSP and were strongly associated with LV late gadolinium enhancement (90%), even in cases of acute myocardial injury with normal ventricular function (4/5, 80% with late gadolinium enhancement). In 4 DSP cases with 18F-fluorodeoxyglucose positron emission tomography scans, acute LV myocardial injury was associated with myocardial inflammation misdiagnosed initially as cardiac sarcoidosis or myocarditis. Left ventricle ejection fraction <55% was strongly associated with severe ventricular arrhythmias for DSP cases (P<0.001, sensitivity 85%, specificity 53%). Right ventricular ejection fraction <45% was associated with severe arrhythmias for PKP2 cases (P<0.001) but was poorly associated for DSP cases (P=0.8). Frequent premature ventricular contractions were common among patients with severe arrhythmias for both DSP (80%) and PKP2 (91%) groups (P=non-significant). CONCLUSIONS: DSP cardiomyopathy is a distinct form of arrhythmogenic cardiomyopathy characterized by episodic myocardial injury, left ventricular fibrosis that precedes systolic dysfunction, and a high incidence of ventricular arrhythmias. A genotype-specific approach for diagnosis and risk stratification should be used.

Prothrombin Complex Concentrate for Emergent Reversal of Intracranial Hemorrhage in Patients with Ventricular Assist Devices.

BACKGROUND: Intracranial hemorrhage (ICH) is a devastating complication for patients with ventricular assist devices (VADs). The safety of emergent anticoagulation reversal with four-factor prothrombin complex concentrate (PCC) and optimal timing of anticoagulation resumption are not clear. In addition, lactate dehydrogenase (LDH) is used as a biomarker for thromboembolic risk, but its utility in guiding anticoagulation management after reversal with PCC has not be described. METHODS: We retrospectively reviewed a consecutive series of patients with VADs presenting with ICH between 2014 and 2020 who received four-factor PCC for rapid anticoagulation reversal. We collected the timing of PCC administration, timing of resumption of anticoagulation, survival, occurrence of thromboembolic events, and LDH levels throughout hospitalization. RESULTS: We identified 16 ICH events in 14 patients with VADs treated with rapid anticoagulation reversal using four-factor PCC (11 intraparenchymal, 4 subdural, 1 subarachnoid hemorrhage). PCC was administered at a mean of 3.3 ± 0.3 h after imaging diagnosis of ICH. Overall mortality was 63%. Survivors had higher presenting Glasgow Coma Scale (median 15, interquartile range [IQR] 15-15 versus 14, IQR 8-14.7, P = 0.041). In all six instances where the patient survived, anticoagulation was resumed on average 9.16 ± 1.62 days after reversal. There were no thromboembolic events prior to resumption of anticoagulation. Three events occurred after anticoagulation resumption and within 3 months of reversal: VAD thrombosis in a patient with thrombosis at the time of reversal, ischemic stroke, and readmission for elevated LDH in the setting of subtherapeutic international normalized ratio. CONCLUSIONS: Our limited series found no thromboembolic complications immediately following anticoagulation reversal with PCC prior to resumption of anticoagulation. LDH trends may be useful to monitor thromboembolic risk after reversal.

Evaluating Biventricular Myocardial Velocity and Interventricular Dyssynchrony in Adult Patients During the First Year After Heart Transplantation.

BACKGROUND: Magnetic resonance tissue phase mapping (TPM) measures three-directional myocardial velocities of the left and right ventricle (LV, RV). This noninvasive technique may supplement endomyocardial biopsy (EMB) in monitoring grafts post-heart transplantation (HTx). PURPOSE: To assess biventricular myocardial velocity alterations in grafts and investigate the relationship between velocities and acute cellular rejection (ACR) episodes. STUDY TYPE: Prospective. SUBJECTS: Twenty-seven patients within 1 year post-HTx (49 ± 13 years, 19 M) and 18 age-matched controls (49 ± 15 years, 12 M). FIELD STRENGTH/SEQUENCE: 1.5T, 2D balanced steady-state free precession, and TPM. ASSESSMENT: Ventricular function: end-diastolic and end-systolic volumes, stroke volumes, ejection fraction (EF), and myocardial mass. TPM velocities: peak-systolic and peak-diastolic velocities, cardiac twist, and interventricular dyssynchrony. ACR rejection episodes: International Society for Heart and Lung Transplantation grading of EMB specimens. STATISTICAL TESTS: The Lilliefors test for normality, unpaired t-tests, and Wilcoxon rank-sum tests for normally and nonnormally distributed data, respectively, were used, as well as multivariate regression for confounding variables and Pearson's correlation for associations between TPM velocities and global function. RESULTS: Compared to controls, HTx patients demonstrated reduced biventricular systolic longitudinal velocities (LV: 5.2 ± 2.1 vs. 4.0 ± 1.5 cm/s, P < 0.05; RV: 4.2 ± 1.3 vs. 3.1 ± 1.2 cm/s, P < 0.01). Correlation analysis revealed significant positive relationships for biventricular EF with radial peak velocities of the same ventricle in both systole and diastole (LV systole: r = 0.48, P < 0.01; LV diastole: r = 0.28, P < 0.05; RV systole: r = 0.35, P < 0.01; RV diastole: r = 0.36, P < 0.01). Segmentally, longitudinal velocities were impaired in 7/16 LV segments and 5/10 RV segments in systole and 7/10 RV segments in diastole. TPM analysis in studies with >4 preceding ACR episodes showed globally reduced RV and LV systolic radial velocity, and segmentally reduced radial and longitudinal systolic velocities. DATA CONCLUSION: Biventricular global and segmental velocities were reduced in HTx patients. Patients with >4 rejection episodes showed reduced myocardial velocities. The TPM sequence may add functional information for monitoring graft dysfunction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:920-929.

Cardiac Structure-Function MRI in Patients After Heart Transplantation.

BACKGROUND: Following heart transplantation (Tx), recipients are closely monitored using endomyocardial biopsy, which is limited by cost and invasiveness, and echocardiography, which is limited regarding detailed structural and functional evaluation. PURPOSE: To test the feasibility of comprehensive structure-function cardiac MRI as a noninvasive modality to assess changes in myocardial structure and function. STUDY TYPE: Prospective. SUBJECTS: MR was performed in 61 heart transplant recipients (age 47.9 ± 16.3 years, 39% female) and 14 age-matched healthy controls (age 47.7 ± 16.7 years, 36% female). FIELD STRENGTH/SEQUENCE: 1.5T; 2D CINE steady state free precession (SSF)P imaging, T2 -mapping, pre- and postgadolinium contrast T1 -mapping, and tissue-phase mapping (TPM). ASSESSMENT: Quantification of myocardial T2 (as a measure of edema), pre- and post-Gd T1 (allowing calculation of extracellular volume (ECV) to estimate interstitial expansion), and TPM-based assessment of peak regional left ventricular (LV) velocities, dyssynchrony, and twist. STATISTICAL TESTS: Comparisons between transplant recipients and controls were performed using independent samples t-tests. Relationships between structural (T2 , T1 , ECV) and functional measures (myocardial velocities, dyssynchrony, twist) were assessed using Pearson correlation analysis. RESULTS: T2 and T1 were significantly elevated in transplant recipients compared to controls (global T2 : 50.5 ± 3.4 msec vs. 45.2 ± 2.3 msec, P < 0.01; global T1 : 1037.8 ± 48.0 msec vs. 993.8 ± 34.1 msec, P < 0.01). Systolic longitudinal function was impaired in transplant recipients compared to controls (reduced peak systolic longitudinal velocities, 2.9 ± 1.1 cm/s vs. 5.1 ± 1.2 cm/s, P < 0.01; elevated systolic longitudinal dyssynchrony, 60.2 ± 30.2 msec vs. 32.1 ± 25.1 msec, P < 0.01). Correlation analysis revealed a significant positive relationship between T2 and ECV (r = 0.45,P < 0.01). In addition, peak systolic longitudinal velocities demonstrated a significant inverse relationship with T2 (global r = -0.29, P = 0.02), and systolic radial dyssynchrony was positively associated with peak T2 and peak T1 (r = 0.26,P = 0.04; r = 0.27,P = 0.03). DATA CONCLUSION: MR techniques are sensitive to structural and functional differences in transplant recipients compared to controls. Structural (T2 , T1 ) and functional (peak myocardial velocities, dyssynchrony) measures were significantly associated, suggesting a structure-function relationship of cardiac abnormalities following heart transplant. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;49:678-687.

Strokes associated with left ventricular assist devices.

Ventricular assist devices (VADs) have improved dramatically over the past several decades but stroke remains a problem. There are multiple etiologies of both ischemic and hemorrhagic strokes associated with VADs. While this problem is yet to be solved, there are continuing efforts at improving the design of VADs to decrease the incidence of stroke and to improve long-term survival in patients requiring mechanical circulatory assistance. The purpose is to review the incidence and underlying causes of stroke in VAD patients.

Effects of Body Mass Index on Presentation and Outcomes of COVID-19 among Heart Transplant and Left Ventricular Assist Device Patients: A Multi-Institutional Study.

The coronavirus disease 2019 (COVID-19) pandemic continues to pose a significant threat to patients receiving advanced heart failure therapies. The current study was undertaken to better understand the relationship between obesity and outcomes of SARS-CoV-2 infection in patients with a left ventricular assist device (LVAD) or heart transplant. We performed a retrospective review of patients with a heart transplant or LVAD who presented to one of the participating 11 institutions between April 1 and November 30, 2020. Patients were grouped by body mass index (BMI) into obese (BMI ≥ 30 k/m2) and nonobese cohorts (BMI < 30 kg/m2). Multivariable logistic regression models were used to estimate effects of obesity on outcomes of interest. Across all centers, 162 heart transplant and 81 LVAD patients were identified; 54 (33%) and 38 (47%) were obese, respectively. Obese patients tended to have more symptoms at presentation. No differences in rates of hospitalization or ICU admission were noted. Obese patients with LVADs were more likely to require mechanical ventilation (39% vs. 8%, p < 0.05). No differences in renal failure or secondary infection were noted. Mortality was similar among heart transplant patients (11% [obese] vs. 16% [nonobese], p = 0.628) and LVAD patients (12% vs. 15%, p = 1.0). BMI was not associated with increased adjusted odds of mortality, ICU admission, or mechanical ventilation (all p > 0.10). In summary, acute presentations of SARS-CoV-2 among heart transplant and LVAD recipients carry a significantly higher mortality than the general population, although BMI does not appear to impact this. Further studies on the longer-term effects of COVID-19 on this population are warranted.

Hyponatremia Is a Powerful Predictor of Poor Prognosis in Left Ventricular Assist Device Patients.

Serum sodium is an established prognostic marker in heart failure (HF) patients and is associated with an increased risk of morbidity and mortality. We sought to study the prognostic value of serum sodium in left ventricular assist device (LVAD) patients and whether hyponatremia reflects worsening HF or an alternative mechanism. We identified HF patients that underwent LVAD implantation between 2008 and 2019. Hyponatremia was defined as Na ≤134 mEq/L at 3 months after implantation. We assessed for differences in hyponatremia before and after LVAD implantation. We also evaluated the association of hyponatremia with all-cause mortality and recurrent HF hospitalizations. There were 342 eligible LVAD patients with a sodium value at 3 months. Among them, there was a significant improvement in serum sodium after LVAD implantation compared to preoperatively (137.2 vs. 134.7 mEq/L, P < 0.0001). Patients with and without hyponatremia had no significant differences in echocardiographic and hemodynamic measurements. In a multivariate analysis, hyponatremia was associated with a markedly increased risk of all-cause mortality (HR 3.69, 95% CI, 1.93-7.05, P < 0.001) when accounting for age, gender, co-morbidities, use of loop diuretics, and B-type natriuretic peptide levels. Hyponatremia was also significantly associated with recurrent HF hospitalizations (HR 2.11, 95% CI, 1.02-4.37, P = 0.04). Hyponatremia in LVAD patients is associated with significantly higher risk of all-cause mortality and recurrent HF hospitalizations. Hyponatremia may be a marker of ongoing neurohormonal activation that is more sensitive than other lab values, echocardiography parameters, and hemodynamic measurements.

Multiparametric Cardiac Magnetic Resonance Imaging Detects Altered Myocardial Tissue and Function in Heart Transplantation Recipients Monitored for Cardiac Allograft Vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a complication beyond the first-year post-heart transplantation (HTx). We aimed to test the utility of cardiac magnetic resonance (CMR) to detect functional/structural changes in HTx recipients with CAV. METHODS: Seventy-seven prospectively recruited HTx recipients beyond the first-year post-HTx and 18 healthy controls underwent CMR, including cine imaging of ventricular function and T1- and T2-mapping to assess myocardial tissue changes. Data analysis included quantification of global cardiac function and regional T2, T1 and extracellular volume based on the 16-segment model. International Society for Heart and Lung Transplantation criteria was used to adjudicate CAV grade (0-3) based on coronary angiography. RESULTS: The majority of HTx recipients (73%) presented with CAV (1: n = 42, 2/3: n = 14, 0: n = 21). Global and segmental T2 (49.5 ± 3.4 ms vs 50.6 ± 3.4 ms, p < 0.001;16/16 segments) were significantly elevated in CAV-0 compared to controls. When comparing CAV-2/3 to CAV-1, global and segmental T2 were significantly increased (53.6 ± 3.2 ms vs. 50.6 ± 2.9 ms, p < 0.001; 16/16 segments) and left ventricular ejection fraction was significantly decreased (54 ± 9% vs. 59 ± 9%, p < 0.05). No global, structural, or functional differences were seen between CAV-0 and CAV-1. CONCLUSIONS: Transplanted hearts display functional and structural alteration compared to native hearts, even in those without evidence of macrovasculopathy (CAV-0). In addition, CMR tissue parameters were sensitive to changes in CAV-1 vs. 2/3 (mild vs. moderate/severe). Further studies are warranted to evaluate the diagnostic value of CMR for the detection and classification of CAV.

Intermittent Occlusion of the Superior Vena Cava to Improve Hemodynamics in Patients With Acutely Decompensated Heart Failure: The VENUS-HF Early Feasibility Study.

BACKGROUND: Reducing congestion remains a primary target of therapy for acutely decompensated heart failure. The VENUS-HF EFS (VENUS-Heart Failure Early Feasibility Study) is the first clinical trial testing intermittent occlusion of the superior vena cava with the preCARDIA system, a catheter mounted balloon and pump console, to improve decongestion in acutely decompensated heart failure. METHODS: In a multicenter, prospective, single-arm exploratory safety and feasibility trial, 30 patients with acutely decompensated heart failure were assigned to preCARDIA therapy for 12 or 24 hours. The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events through 30 days. Secondary end points included technical success defined as successful preCARDIA placement, treatment, and removal and reduction in right atrial and pulmonary capillary wedge pressure. Other efficacy measures included urine output and patient-reported symptoms. RESULTS: Thirty patients were enrolled and assigned to receive the preCARDIA system. Freedom from device- or procedure-related major adverse events was observed in 100% (n=30/30) of patients. The system was successfully placed, activated and removed after 12 (n=6) or 24 hours (n=23) in 97% (n=29/30) of patients. Compared with baseline values, right atrial pressure decreased by 34% (17±4 versus 11±5 mm Hg, P<0.001) and pulmonary capillary wedge pressure decreased by 27% (31±8 versus 22±9 mm Hg, P<0.001). Compared with pretreatment values, urine output and net fluid balance increased by 130% and 156%, respectively, with up to 24 hours of treatment (P<0.01). CONCLUSIONS: We report the first-in-human experience of intermittent superior vena cava occlusion using the preCARDIA system to reduce congestion in acutely decompensated heart failure. PreCARDIA treatment for up to 24 hours was well tolerated without device- or procedure-related serious or major adverse events and associated with reduced filling pressures and increased urine output. These results support future studies characterizing the clinical utility of the preCARDIA system. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03836079.

Association of cigarette smoking and adverse events in left ventricular assist device patients.

INTRODUCTION: Adverse events (AEs) associated with left ventricular assist devices (LVADs) cause significant morbidity and mortality. Little is known about patient-specific factors that contribute to rates of AEs. The purpose of this study was to assess the association of cigarette smoking history and AEs following LVAD implantation. METHODS: This study was a single-center, observational examination of 355 consecutive patients who underwent continuous-flow LVAD implantation from May 1, 2008 to July 1, 2018. Based on self-report, 348 patients with available data were categorized as never, former, or current smokers. Pre-LVAD implantation baseline characteristics were obtained, and summary characteristics were calculated. Hospitalizations for gastrointestinal bleeds, driveline infections, strokes, pump thromboses, and acute heart failure were evaluated. The Cox proportional hazard model was used to estimate the association of smoking and AE-related hospital admissions. The cumulative incidence competing risk method was used for survival analysis. RESULTS: Current (8.22%, p 0.006) and former (4.75%, p 0.026) smokers had a greater proportion of admissions for pump thrombosis compared to never smokers (2.22%). Former smoking was associated with admission for driveline infection (HR 2.43, CI 1.08-5.46, p 0.03) on multivariate analysis. There were no significant associations between smoking and the other AEs of interest. There was no difference in survival among the three groups. CONCLUSIONS: Smokers had a higher proportion of admissions for pump thrombosis compared to never smokers, and former smoking was associated with admission for driveline infections in patients with LVADs.

Fulminant myocarditis in a patient with coronavirus disease 2019 and rapid myocardial recovery following treatment.

Coronavirus disease 2019 (COVID-19) is a global pandemic increasingly encountered in the clinical setting. It typically manifests as a respiratory illness, although cardiac involvement is common and portends a worse prognosis. We present the case of a 56-year-old male admitted with COVID-19 fulminant myocarditis and cardiogenic shock. We discuss important aspects of the multidisciplinary and interventional care involved in treating cardiogenic shock as well as the likely mechanisms of, and potential treatment for, COVID-19 myocarditis. The various pathways of myocardial injury, including direct viral damage, macrophage activation, and lymphocytic infiltration, are outlined in detail in addition to associated pathology such as cytokine release syndrome. COVID-19 is a complex and multisystem disease process; in addition to supportive care, specific consideration should be given to the underlying mechanism of injury for each patient.

Prognostic Value of Myocardial Extracellular Volume Fraction and T2-mapping in Heart Transplant Patients.

OBJECTIVES: The purpose of this study was to examine prognostic value of T1- and T2-mapping techniques in heart transplant patients. BACKGROUND: Myocardial characterization using T2 mapping (evaluation of edema/inflammation) and pre- and post-gadolinium contrast T1 mapping (calculation of extracellular volume fraction [ECV] for assessment of interstitial expansion/fibrosis) are emerging modalities that have been investigated in various cardiomyopathies. METHODS: A total of 99 heart transplant patients underwent the magnetic resonance imaging (MRI) scans including T1- (n = 90) and T2-mapping (n = 79) techniques. Relevant clinical characteristics, MRI parameters including late gadolinium enhancement (LGE), and invasive hemodynamics were collected. Median clinical follow-up duration after the baseline scan was 2.4 to 3.5 years. Clinical outcomes include cardiac events (cardiac death, myocardial infarction, coronary revascularization, and heart failure hospitalization), noncardiac death and noncardiac hospitalization. RESULTS: Overall, the global native T1, postcontrast T1, ECV, and T2 were 1,030 ± 56 ms, 458 ± 84 ms, 27 ± 4% and 50 ± 4 ms, respectively. Top-tercile-range ECV (ECV >29%) independently predicted adverse clinical outcomes compared with bottom-tercile-range ECV (ECV <25%) (hazard ratio [HR]: 2.87; 95% confidence interval [CI]: 1.07 to 7.68; p = 0.04) in a multivariable model with left ventricular end-systolic volume and LGE. Higher T2 (T2 ≥50.2 ms) independently predicted adverse clinical outcomes (HR: 3.01; 95% CI: 1.39 to 6.54; p = 0.005) after adjustment for left ventricular ejection fraction, left ventricular end-systolic volume, and LGE. Additionally, higher T2 (T2 ≥50.2 ms) also independently predicted cardiac events (HR: 4.92; CI: 1.60 to 15.14; p = 0.005) in a multivariable model with left ventricular ejection fraction. CONCLUSIONS: MRI-derived myocardial ECV and T2 mapping in heart transplant patients were independently associated with cardiac and noncardiac outcomes. Our findings highlight the need for larger prospective studies.

Impact of Hemodynamic Ramp Test-Guided HVAD Speed and Medication Adjustments on Clinical Outcomes.

BACKGROUND: Hemodynamic ramp (HR) tests can guide the optimization of left ventricular assist device (LVAD) speed and direct medical therapy. We investigated the effects of HR-guided LVAD management. METHODS AND RESULTS: This prospective, multicenter, randomized, pilot study compared outcomes in LVAD patients using an HR-guided (HR group) versus a standard transthoracic echocardiography-guided (control group) management strategy. Patients were enrolled and randomized 1 to 3 months post-HVAD implantation and followed for 6 months. Twenty-two patients (57±10 years, 73% male) were randomized to the HR group and 19 patients (51±13 years, 63% male) to the control group. HR group patients had double the number of LVAD speed changes (1.68 versus 0.84 changes/patient, P=0.09 with an incidence rate ratio 2.0, 95% CI, 0.9-4.7) with twice the magnitude of rotations per minute changes (130 versus 60 rotations per minute/patient, P=0.004) during the study. The HR group also had 2-fold greater heart failure medication changes (4.32 versus 2.53 changes/patient, P=0.072, incidence rate ratio 1.7 with 95% CI, 0.8-3.5) predominantly because of changes in diuretic dose (40 versus 0 mg/patient, P<0.001). The HR group had numerically but not statistically higher event-free survival (62% versus 46%, P=0.087; hazard ratio, 0.46 with 95% CI, 0.2-1.2), with numerically but not statistically lower events per patient-year ( P=0.084). There were no significant differences in the 6-minute walk or Kansas City Cardiomyopathy Questionnaire tests at 6 months. CONCLUSIONS: In this randomized pilot study of LVAD patient management we demonstrated the feasibility of standardized HR testing at multiple institutions and that a strategy guided by hemodynamics was associated with more LVAD speed and medication adjustments and a nonsignificant reduction in adverse events. A pivotal study to demonstrate the clinical benefit of HR testing is warranted. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03021239.

Multiparametric Cardiac Magnetic Resonance Imaging Can Detect Acute Cardiac Allograft Rejection After Heart Transplantation.

OBJECTIVES: The purpose of this study was to evaluate the sensitivity of multiparametric cardiac magnetic resonance imaging (CMR) for the detection of acute cardiac allograft rejection (ACAR). BACKGROUND: ACAR is currently diagnosed by endomyocardial biopsy, but CMR may be a noninvasive alternative because of its capacity for regional myocardial structure and function characterization. METHODS: Fifty-eight transplant recipients (mean age 47.0 ± 14.7 years) and 14 control subjects (mean age 47.7 ± 16.7 years) were prospectively recruited from August 2014 to May 2017 and underwent 97 CMR studies (83 transplant recipients, 14 control subjects) for assessment of global left ventricular function and myocardial T2, T1, and extracellular volume fraction (ECV). CMR studies were divided into 4 groups on the basis of biopsy grade: control subjects (n = 14), patients with no ACAR (no history of ACAR; n = 36), patients with past ACAR (history of ACAR; n = 24), and ACAR+ patients (active grade ≥1R ACAR; n = 23). RESULTS: Myocardial T2 was significantly higher in patients with past ACAR compared with those with no ACAR (51.0 ± 3.8 ms vs. 49.2 ± 4.0 ms; p = 0.02) and in patients with no ACAR compared with control subjects (49.2 ± 4.0 ms vs. 45.2 ± 2.3 ms; p < 0.01). ACAR+ patients demonstrated increased T2 compared with the no ACAR group (52.4 ± 4.7 ms vs. 49.2 ± 4.0 ms, p < 0.01) but not compared with the past ACAR group. In contrast, ECV was significantly elevated in ACAR+ patients compared with transplant recipients without ACAR regardless of history of ACAR (no ACAR: 31.5 ± 3.9% vs. 26.8 ± 3.3% [p < 0.01]; past ACAR: 31.5 ± 3.9% vs. 26.8 ± 4.0% [p < 0.01]). Receiver operating characteristic curve analysis revealed that a combined model of age at CMR, global T2, and global ECV was predictive of ACAR (area under the curve = 0.84). CONCLUSIONS: The combination of CMR-derived myocardial T2 and ECV has potential as a noninvasive tissue biomarker for ACAR. Larger studies during acute ACAR are needed for continued development of multiparametric CMR for transplant recipient surveillance.

Donor and Recipient Characteristics in Heart Transplantation Are Associated with Altered Myocardial Tissue Structure and Cardiac Function.

PURPOSE: To use structure-function cardiac MRI in the evaluation of relationships between donor and heart transplantation (HTx) recipient characteristics and changes in cardiac tissue structure and function. HTx candidates and donor hearts are evaluated for donor-recipient matches to improve survival, but the impact of donor and recipient characteristics on changes in myocardial tissue and function in the transplanted heart is not fully understood. MATERIALS AND METHODS: Cardiac MRI at 1.5 T was performed from August 2014 to June 2017 in 58 HTx recipients (mean age, 51.1 years ± 12.6 [standard deviation], 26 female patients) and included T2 mapping (to evaluate edematous and/or inflammatory changes), precontrast and postcontrast T1 mapping (allowing the calculation of extracellular volume fraction [ECV] to estimate interstitial expansion), and tissue phase mapping (allowing the calculation of myocardial velocities and twist). Donor and recipient demographics (age, sex, height, weight, and body mass index [BMI]) and comorbidities (hypertension, diabetes, and smoking history) were evaluated for relationships with cardiac MRI measures. RESULTS: Sex-influenced cardiac MRI measures of myocardial tissue and function are as follows: Female HTx recipients demonstrated increased precontrast T1 (P = .002) and reduced systolic peak long-axis velocities (P = .015). Increased age of the donor heart was associated with elevated T2 (r = 0.32; P < .05) and ECV (r = 0.47; P < .01), indicating increased edema and interstitial expansion, as well as impaired diastolic peak long-axis velocities (r = 0.41; P < .01). Recipient-donor differences in age, weight, and BMI were significantly associated with elevated ECV (r = 0.36-0.48; P < .05). Hypertension in donors resulted in increased ECV (31.0% ± 4.2 vs 26.0% ± 3.3; P = .001). CONCLUSION: Donor and HTx recipient characteristics were significantly associated with cardiac MRI-derived measures of myocardial tissue structure and function.© RSNA, 2019.

Comparison of matrix metalloproteinase 9 and brain natriuretic peptide as clinical biomarkers in chronic heart failure.

BACKGROUND: Matrix metalloproteinase 9 (MMP-9) may serve as a biomarker of ventricular remodeling in selected populations, but few studies have assessed its performance in clinical practice. We tested MMP-9 as a biomarker of remodeling and predictor of outcomes in a systolic heart failure cohort derived from clinical practice and compared its performance to brain natriuretic peptide (BNP). METHODS: Plasma MMP-9 and BNP levels were measured in 395 outpatients with systolic heart failure who participated in the Penn Heart Failure Study. We tested for (1) cross-sectional associations between biomarker levels, left ventricular end-diastolic dimension index (LVEDDI), and ejection fraction (EF), and (2) associations between baseline biomarker levels and risk of subsequent cardiac hospitalization or death over 3 years of follow-up. RESULTS: Matrix metalloproteinase 9 had no significant correlation with LVEDDI (rho = 0.04, P = not significant) or EF (rho = -0.06, P = not significant), whereas BNP showed highly significant correlations (LVEDDI: rho = -0.27, P < .0001; EF: rho = -0.35, P < .0001). In multivariate linear regression models, MMP-9 again showed no significant associations with LVEDDI (P = .6) or EF (P = .14), whereas BNP showed strong independent associations (LVEDDI: P < .001; EF: P = .002). Kaplan-Meier analyses showed no difference in hospital-free survival by baseline MMP-9 tertile (P = .7), whereas higher BNP tertile predicted worse survival (P < .0001). In multivariate Cox models, baseline MMP-9 level did not predict risk of adverse outcome (hazard ratio for log increase 0.98, P = .9), whereas BNP was a significant independent predictor (hazard ratio for log increase 1.15, P = .02). CONCLUSION: Compared to BNP, MMP-9 is a poor clinical biomarker of remodeling and outcome in patients with systolic heart failure derived from clinical practice.

Baseline Longitudinal Strain Predicts Recovery of Left Ventricular Ejection Fraction in Hospitalized Patients With Nonischemic Cardiomyopathy.

Background Heart failure ( HF ) with "recovered" ejection fraction ( HF rec EF ) is an emerging phenotype, but no tools exist to predict ejection fraction ( EF ) recovery in acute HF . We hypothesized that indices of baseline cardiac structure and function predict HF rec EF in nonischemic cardiomyopathy and reduced EF . Methods and Results We identified a nonischemic cardiomyopathy cohort with EF <40% during the first HF hospitalization (n=166). We performed speckle-tracking echocardiography to measure longitudinal, circumferential, and radial strain, and the average of these measures (myocardial systolic performance). HF rec EF was defined as follow-up EF ≥40% and ≥10% improvement from baseline EF . Fifty-nine patients (36%) achieved HF rec EF (baseline EF 26±7%; follow-up EF 51±7%) within a median of 135 (interquartile range 58-239) days after the first HF hospitalization. Baseline demographics, biomarker profiles, and comorbid conditions (except lower chronic kidney disease in HF rec EF ) were similar between HF rec EF and persistent reduced- EF groups. HF rec EF patients had smaller baseline left ventricular end-systolic dimension (3.6 versus 4.8 cm; P<0.01), higher baseline myocardial systolic performance (9.2% versus 8.1%; P=0.02), and improved survival (adjusted hazard ratio 0.27, 95% confidence interval 0.11, 0.62). We found a significant interaction between baseline left ventricular end-systolic dimension and absolute longitudinal strain. Among patients with left ventricular end-systolic dimension >4.35 cm, higher absolute longitudinal strain (≥8%) was associated with HF rec EF (unadjusted odds ratio=3.9, 95% CI )confidence interval 1.2, 12.8). Incorporation of baseline indices of cardiac mechanics with clinical variables resulted in a predictive model for HF rec EF with c-statistic=0.85. Conclusions Factors associated with achieving HF rec EF were specific to cardiac structure and indices of cardiac mechanics. Higher baseline absolute longitudinal strain is associated with HF rec EF among nonischemic cardiomyopathy patients with reduced EF and larger left ventricular dimensions.

Clinical echocardiographic indices of left ventricular diastolic function correlate poorly with pulmonary capillary wedge pressure at 1 year following heart transplantation.

Clinical echocardiographic assessment of left ventricular (LV) systolic and diastolic function is routinely performed following orthotopic heart transplantation (OHT). The purpose of this study was to determine whether echocardiographic indices of LV diastolic function correlate with pulmonary capillary wedge pressure (PCWP) in the transplanted heart. Patients who had OHT between June 2009 and November 2011 underwent transthoracic echocardiography and right heart catheterization (RHC) at approximately 1 year post transplantation. We retrospectively assessed 33 potential parameters of LV diastolic function using 2-dimensional, spectral Doppler and tissue Doppler echocardiography. We measured PCWP by RHC. We compared echocardiographic measures with PCWP using linear regression analysis. Ninety-five patients (mean age 49 ± 13 years, 73 males, mean LV ejection fraction 62 ± 10%) were included in the study. Overall, echocardiographic parameters of LV diastolic function demonstrated poor correlation with PCWP. By linear regression, the parameter that most strongly correlated with PCWP was left atrial (LA) minimum area in the apical 4-chamber view (p = 0.002, r(2) = 0.1). Comparing patients with PCWP ≤ 12 mmHg and those with PCWP > 12 mmHg, the parameter that demonstrated the most significant difference was LA minimum area in the apical 2-chamber view (p = 0.002), and comparing patients with PCWP ≤ 15 mmHg and those with PCWP > 15 mmHg, the most significant difference was peak early diastolic velocity of the mitral annulus (p = 0.02). In patients with cardiac allografts, clinical echocardiographic measures of LV diastolic function correlate poorly with PCWP.