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.

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.

Time Spent Engaging in Health Care Among Patients With Left Ventricular Assist Devices.

OBJECTIVES: This study aims to examine a novel patient-centered metric of time spent engaging in left ventricular assist device (LVAD)-related clinical care outside the home. BACKGROUND: Although LVAD implantation can improve survival and functional capacity in patients with advanced heart failure, this may occur at the expense of significant time spent engaging in LVAD-related health care activities. METHODS: The authors retrospectively assessed consecutive patients at a single center who received a continuous-flow LVAD between May 9, 2008, and December 31, 2019, and queried health care encounters after implantation, including all inpatient encounters and LVAD-related ambulatory encounters. Patient-level time metrics were determined, including the total number of days with any health care encounter, and the total estimated time spent receiving care. The primary outcome was the proportion (%) of days alive with an LVAD spent engaged in at least 1 health care encounter. The secondary outcome was the proportion (%) of total time alive with an LVAD spent receiving care. RESULTS: Among 373 patients, the median number of days alive with LVAD was 390 (IQR: 158-840 days). Patients had a median number of 88 (IQR: 45-161) days with ≥1 health care encounter, accounting for 23.2% (IQR: 16.3%-32.4%) of their days alive with an LVAD. A median 6.0% (IQR: 2.1%-14.1%) and 15.0% (IQR: 10.7%-20.0%) of total days alive were spent in inpatient and ambulatory encounters, respectively. Patients spent a median of 592 (IQR: 197-1,257) hours receiving care, accounting for 5.6% (IQR: 2.2%-12.7%) of their total time alive with an LVAD. CONCLUSIONS: LVAD patients spent more than 1 of every 5 days engaging in health care. Our findings may inform strategies to improve efficiency of postdischarge care delivery and expectations for post-treatment care.

Risk of Renal Dysfunction Following Heart Transplantation in Patients Bridged with a Left Ventricular Assist Device.

Acute renal failure (ARF) and chronic kidney disease (CKD) are associated with short- and long-term morbidity and mortality following heart transplantation (HT). We investigated the incidence and risk factors for developing ARF requiring hemodialysis (HD) and CKD following HT specifically in patients with a left ventricular assist device (LVAD). We examined the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry for heart transplant patients between January 2000 and June 2015. We compared patients bridged with durable continuous-flow LVAD to those without LVAD support. Primary outcomes were ARF requiring HD before discharge following HT and CKD (defined as creatinine >2.5 mg/dl, permanent dialysis, or renal transplant) within 3 years. There were 18,738 patients, with 4,535 (24%) bridged with LVAD support. Left ventricular assist device patients had higher incidence of ARF requiring HD and CKD at 1 year, but no significant difference in CKD at 3 years compared to non-LVAD patients. Among LVAD patients, body mass index (BMI) (odds ratio [OR] = 1.79, p < 0.001), baseline estimated glomerular filtration rate (eGFR) (OR = 0.43, p < 0.001), and ischemic time (OR = 1.28, p = 0.014) were significantly associated with ARF requiring HD. Similarly, BMI (hazard ratio [HR] = 1.49, p < 0.001), baseline eGFR (HR = 0.41, p < 0.001), pre-HT diabetes mellitus (DM) (HR = 1.37, p = 0.011), and post-HT dialysis before discharge (HR = 3.93, p < 0.001) were significantly associated with CKD. Left ventricular assist device patients have a higher incidence of ARF requiring HD and CKD at 1 year after HT compared with non-LVAD patients, but incidence of CKD is similar by 3 years. Baseline renal function, BMI, ischemic time, and DM can help identify LVAD patients at risk of ARF requiring HD or CKD following HT.

Colonization with Multidrug-resistant Organisms in Patients with Ventricular Assist Devices.

Infection is a leading cause of morbidity and mortality in patients with ventricular assist devices (VAD). The impact of colonization with multidrug-resistant organisms (MDRO) on outcomes in this cohort is unknown. Patients on VAD support from July 2008 to September 2018 at a single site were evaluated for MDRO colonization after implantation. MDROs included methicillin-resistant Staphylococcus aureus , vancomycin-resistant Enterococcus species, and extended-spectrum beta-lactamase producing gram-negative bacteria. 378 patients with 433 VADs were included. 42.6% (n = 161) of patients were colonized with an MDRO throughout the duration of VAD support. Eighty-two VAD infections occurred, 74.4% (n = 61) of whom were MDRO colonized before infection. MDRO colonization was associated with an increased risk of a subsequent VAD infection (hazard ratio 3.704, p < 0.001). MDRO colonization is common after VAD implantation and is associated with future VAD infections. Further study is needed to determine best management strategies for VAD recipients with MDRO colonization given this increased risk.

Augmented Intelligence to Identify Patients With Advanced Heart Failure in an Integrated Health System.

BACKGROUND: Timely referral for specialist evaluation in patients with advanced heart failure (HF) is a Class 1 recommendation. However, the transition from stage C HF to advanced or stage D HF often goes undetected in routine care, resulting in delayed referral and higher mortality rates. OBJECTIVES: The authors sought to develop an augmented intelligence-enabled workflow using machine learning to identify patients with stage D HF and streamline referral. METHODS: We extracted data on HF patients with encounters from January 1, 2007, to November 30, 2020, from a HF registry within a regional, integrated health system. We created an ensemble machine learning model to predict stage C or stage D HF and integrated the results within the electronic health record. RESULTS: In a retrospective data set of 14,846 patients, the model had a good positive predictive value (60%) and low sensitivity (25%) for identifying stage D HF in a 100-person, physician-reviewed, holdout test set. During prospective implementation of the workflow from April 1, 2021, to February 15, 2022, 416 patients were reviewed by a clinical coordinator, with agreement between the model and the coordinator in 50.3% of stage D predictions. Twenty-four patients have been scheduled for evaluation in a HF clinic, 4 patients started an evaluation for advanced therapies, and 1 patient received a left ventricular assist device. CONCLUSIONS: An augmented intelligence-enabled workflow was integrated into clinical operations to identify patients with advanced HF. Endeavors such as this require a multidisciplinary team with experience in design thinking, informatics, quality improvement, operations, and health information technology, as well as dedicated resources to monitor and improve performance over time.

A Power Tracking Algorithm for Early Detection of Centrifugal Flow Pump Thrombosis.

Logfiles from the HeartWare HVAD System provide operational pump trend data to aid in patient management. Pump thrombosis is commonly associated with increases in the logfile power that may precede the clinical presentation. A Power Tracking algorithm was developed to detect significant deviations in pump power that may be associated with pump thrombus (PT). The Power Tracking algorithm was applied retrospectively to logfiles captured in the ENDURANCE, ENDURANCE Supplemental, and LATERAL clinical trials. From a combined dataset of 896 patients, available logfiles with suspected PT (n = 70 events in 60 patients) and available logfiles from patients without adverse events (AEs) (n = 106 patients, consisting of 27.4 patient-years of monitoring) were organized into two cohorts. The Power Tracking algorithm detected PT cases on or before the recorded AE date with a sensitivity of 85.7%, with detection occurring an average of 3.9 days before clinical presentation. The algorithm averaged one false alarm for every 6.85 patient-years of monitoring from logfiles without AEs. The favorable performance of the Power Tracking algorithm may enable earlier detection of pump thrombosis and allow early medical management versus surgical intervention.

Levosimendan Improves Hemodynamics and Exercise Tolerance in PH-HFpEF: Results of the Randomized Placebo-Controlled HELP Trial.

OBJECTIVES: The purpose of this study was to evaluate the effects of intravenous levosimendan on hemodynamics and 6-min walk distance (6MWD) in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF). BACKGROUND: There are no proven effective treatments for patients with PH-HFpEF. METHODS: Patients with mean pulmonary artery pressure (mPAP) ≥35 mm Hg, pulmonary capillary wedge pressure (PCWP) ≥20 mm Hg, and LVEF ≥40% underwent 6MWD and hemodynamic measurements at rest, during passive leg raise, and supine cycle exercise at baseline and after an open-label 24-h levosimendan infusion (0.1 µg/kg/min). Hemodynamic responders (those with ≥4 mm Hg reduction of exercise-PCWP) were randomized (double blind) to weekly levosimendan infusion (0.075 to 0.1 ug/kg/min for 24 h) or placebo for 5 additional weeks. The primary end point was exercise-PCWP, and key secondary end points included 6MWD and PCWP measured across all exercise stages. RESULTS: Thirty-seven of 44 patients (84%) met responder criteria and were randomized to levosimendan (n = 18) or placebo (n = 19). Participants were 69 ± 9 years of age, 61% female, and with resting mPAP 41.0 ± 9.3 mm Hg and exercise-PCWP 36.8 ± 11.3 mm Hg. Compared with placebo, levosimendan did not significantly reduce the primary end point of exercise-PCWP at 6 weeks (-1.4 mm Hg; 95% confidence interval [CI]: -7.8 to 4.8; p = 0.65). However, levosimendan reduced PCWP measured across all exercise stages (-3.9 ± 2.0 mm Hg; p = 0.047). Levosimendan treatment resulted in a 29.3 m (95% CI: 2.5 to 56.1; p = 0.033) improvement in 6MWD compared with placebo. CONCLUSIONS: Six weeks of once-weekly levosimendan infusion did not affect exercise-PCWP but did reduce PCWP incorporating data from rest and exercise, in tandem with increased 6MWD. Further study of levosimendan is warranted as a therapeutic option for PH-HFpEF. (Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF [HELP]; NCT03541603).

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.

Obesity and Outcomes Following Cardiogenic Shock Requiring Acute Mechanical Circulatory Support.

BACKGROUND: The association of obesity on outcomes in patients with cardiogenic shock requiring acute mechanical circulatory support has not been thoroughly investigated. METHODS: We evaluated the National Readmission Database for adults with either acute myocardial infarction or heart failure complicated by cardiogenic shock requiring acute mechanical circulatory support between January 2016 and November 2017. Exposure was assessed using International Classification of Diseases, Tenth Revision codes for the degree of obesity with the reference being body mass index (BMI) of 20.0 to 29.9 group. Multiple logistic regression and Cox regression analysis were used to analyze in-hospital mortality and 30-day readmission, respectively. RESULTS: The survey-weighted sample included a total of 35 555 hospitalizations with a mean age of 65.4±0.2 years and 29.8% females. Obesity was associated with higher in-hospital mortality (no obesity, 26.4% [BMI, 20.0-29.9] versus class I obesity, 25.0% [BMI, 30.0-34.9] versus class II obesity, 28.7% [BMI, 35.0-39.9] versus class III obesity, 34.9% [BMI, ≥40]; P<0.001). On stratified analysis, compared with a nonobese phenotype, younger adults (age <60) with class II and class III obesity (odds ratio, 1.9 [95% CI, 1.1-3.5], P=0.02; odds ratio, 2.1 [95% CI, 1.2-3.7], P=0.01) and older adults (age ≥60) with class III obesity (odds ratio, 1.7 [95% CI, 1.2-2.4], P=0.005) had higher mortality. There was no association between the degree of obesity and 30-day readmission. CONCLUSIONS: Among adults with acute myocardial infarction or acute heart failure resulting in cardiogenic shock requiring acute mechanical circulatory support, younger adults with class II and class III obesity and older patients with class III obesity have a higher risk of in-hospital mortality compared with nonobese patients.

Cardiac transplantation outcomes in patients with amyloid cardiomyopathy.

OBJECTIVE: Amyloid cardiomyopathy (ACM) is a progressive and life-threatening disease caused by abnormal protein deposits within cardiac tissue. The most common forms of ACM are caused by immunoglobulin derived light chains (AL) and transthyretin (TTR). Orthotopic heart transplantation (OHT) remains the definitive treatment for patients with end stage heart failure. In this study, we perform a contemporary multicenter analysis evaluating post OHT survival in patients with ACM. METHODS: We conducted a multicenter analysis of 40,044 adult OHT recipients captured in the United Network for Organ Sharing (UNOS) registry from 1987-2018. Patients were characterized as ACM or non-ACM. Baseline characteristics were obtained, and summary characteristics were calculated. Outcomes of interest included post-transplant survival, infection, treated rejection, and the ability to return to work. Racial differences in OHT survival were also analyzed. Unadjusted associations between ACM and non-ACM survival were determined using the Kaplan-Meier estimations and confounding was addressed using multivariable Cox proportional hazards models. RESULTS: Three hundred ninety-eight patients with a diagnosis of ACM were identified of which 313 underwent heart only OHT. ACM patients were older (61 vs 53; P < .0001) and had a higher proportion of African Americans (30.7% vs 17.6%; P < .0001). Median survival for ACM was 10.2 years vs 12.5 years in non-ACM (P = .01). After adjusting for confounding, ACM patients had a higher likelihood of death post-OHT (HR 1.39 CI: 1.14, 1.70; P = .001). African American ACM patients had a higher likelihood of survival compared to White ACM patients (HR 0.51 CI 0.31-0.85; P = .01). No difference was observed in episodes of treated rejection (OR 0.63 CI 0.23, 1.78; P = .39), hospitalizations for infections (OR 1.24 CI: 0.85, 1.81; P = .26), or likelihood of returning to work for income (OR 1.23 CI: 0.84, 1.80; P = .30). CONCLUSIONS: In this analysis of OHT in ACM, ACM was associated with a higher likelihood of post-OHT mortality. Racial differences in post-OHT were observed with African American patients with ACM having higher likelihood of survival compared to White patients with ACM. No differences were observed in episodes of treated rejection, hospitalization for infection, or likelihood to return to work for income.

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.

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.

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.

Management and outcome of intracranial hemorrhage in patients with left ventricular assist devices.

OBJECTIVE: As the use of left ventricular assist devices (LVADs) has expanded, cerebrovascular complications have become an increasing source of morbidity and mortality in this population. Intracranial hemorrhage (ICH) in particular remains a devastating complication in patients who undergo LVAD placement with no defined management guidelines. The authors therefore reviewed surgical and anticoagulation management and outcomes of patients with LVADs who presented to their institution with ICH. METHODS: This retrospective cohort study assessed outcomes of patients who underwent LVAD placement at a single institution between 2007 and 2016 and in whom imaging demonstrated ICH. RESULTS: During the study period, 281 patients had a HeartMate II or HeartWare LVAD placed. There were 37 episodes of ICH (recurrent in 3 cases). ICHs were categorized as intraparenchymal hemorrhage (IPH; n = 22, 59%), subdural hemorrhage (SDH; n = 6, 16%), and subarachnoid hemorrhage (SAH; n = 9, 24%). Neurosurgical intervention was deemed necessary in 27.3%, 66.7%, and 0% of patients with IPH, SDH, and SAH, respectively; overall survival > 30 days for each type of hemorrhage was 41%, 83%, and 89%, respectively. No patients had LVAD thrombus as a result of reversal of anticoagulation. Combined with prior reports, good outcomes are seen more often following surgery for SDH than for IPH (57% vs 7%, p = 0.004) in patients who underwent VAD placement. CONCLUSIONS: Patients with IPH who undergo LVAD placement have poor outcomes regardless of anticoagulation reversal or neurosurgical intervention, whereas those with SDH may have good outcomes with medical and surgical intervention, and those with SAH appear to do well without anticoagulation reversal or surgery. When needed, anticoagulation reversal was not associated with an increase in LVAD thrombosis in this series.

LVAD with concomitant rapid deployment valve implantation - a case report.

BACKGROUND: Aortic valve insufficiency can have significant hemodynamic consequences for patients with left ventricular assist devices. A circulation loop can limit systemic blood flow and increase left ventricular filling pressure. CASE PRESENTATION: A 64-year-old male with non-ischemic dilated cardiomyopathy underwent Heartware™ HVAD left ventricular assist device implantation with successful concomitant aortic valve replacement with an Edwards Intuity rapid deployment prosthetic valve. CONCLUSIONS: The use of this rapid deployment valve may have benefits over other techniques including shorter cross clamp times during surgery, intermediate-long term durability, and preservation of aortic valve opening to allow for potential ventricular recovery. The Intuity rapid deployment valve should thus be considered a viable and suitable option for aortic insufficiency intervention during LVAD implantation.

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.