Residual or recurrent mitral regurgitation predicts mortality following transcatheter edge-to-edge mitral valve repair.

Objective: Although regurgitant mitral valves can be repaired through surgical or transcatheter approaches, contemporary comparative outcomes are limited with the impact of residual and recurrent mitral regurgitation (MR) on clinical outcomes being poorly defined. We hypothesized that moderate (2+) or greater residual or recurrent (RR) MR-regardless of type of repair-predicts worse clinical outcomes. Methods: Our institutional experience of 660 consecutive patients undergoing mitral valve repair (2015-2021) consisting of 393 surgical mitral valve repair (SMVr) and 267 transcatheter edge-to-edge mitral valve repair (TEER) was studied. The echocardiographic impact of RRMR (2+) following both SMVr and TEER on death and reintervention was evaluated. Results: Patients averaged 67.8 ± 14.2 years (SMVr = 63.8 ± 13.3 vs 73.6 ± 13.6, P < .0001) and 62.1% were male. Baseline clinical and demographic data were vastly different between the 2 groups. Residual or recurrent 2+ or greater MR developed in 25% (n = 68) of patients who received TEER compared with 6% (n = 25) of SMVr (P < .0001). Reintervention (9.3% vs 2.4%, P = .002) and death (37.9% vs 10.4%, P < .0001) rates at 3-years were greater among the TEER group versus SMVr group. Given the heterogeneity in baseline characteristics and difference in survival, each cohort was analyzed separately, stratified by RRMR, using multivariable modeling to identify predictors of repeat reintervention and death. There were too few events of RRMR in the SMVr cohort for evaluation. For the TEER subgroups, we observed greater long-term mortality, but not reintervention among those with RRMR., Hypertension was the strongest predictor of death and obesity was for reintervention. Conclusions: Patients undergoing SMVr and TEER are vastly different with respect to baseline patient characteristics and clinical outcomes, with patients who undergo TEER being much greater risk with poorer prognosis. Moderate or greater RRMR predicted worse long-term survival but not reintervention among patients who received TEER. Given the difference in survival among patients with RRMR following TEER, care must be taken to ensure that patients entering clinical trials and receiving TEER should have a high probability of achieving mild or less MR as seen in contemporary surgical results.

The Impact of Adverse Events on Functional Capacity and Quality of Life After HeartWare Ventricular Assist Device Implantation.

Left ventricular assist devices (LVADs) improve quality of life (QoL) and functional capacity (FC) for patients with advanced heart failure. The association between adverse events (AEs) and changes in QoL and FC are unknown. Patients treated with the HeartWare ventricular assist device (HVAD) with paired 6-minute walk distance (6MWD, n = 263) and Kansas City Cardiomyopathy Questionnaires (KCCQ, n = 272) at baseline and 24 months in the ENDURANCE and ENDURANCE Supplemental Trial databases were included. Patients were stratified based upon occurrence of clinically significant AEs during the first 24 months of support and analyzed for the mean change in 6MWD and KCCQ. The impact of AE frequency on change in 6MWD and KCCQ from baseline to 24 months was evaluated. Of the AEs examined, only sepsis was associated with an improvement in 6MWD (109 m vs. 16 m, p = 0.002). Patients without improvement in 6MWD test from baseline to 24 months had significantly more AEs than those with FC improvement (p = 0.0002). Adverse events did not affect the KCCQ overall summary score. In this analysis, patients with fewer AEs had greater improvement in FC during the 24-month follow up. The frequency of AEs did not have a significant impact on QoL after LVAD implantation.

Transcatheter mitral valve in ring, hazards of long anterior mitral leaflet and 3-dimensional rings.

OBJECTIVES: The purpose of this study was to define anterior mitral leaflet (AML) length and mitral ring characteristics associated with LVOT obstruction and PVL following MViR. BACKGROUND: Transcatheter Mitral Valve in Ring (MViR) procedural complications including parvalvular leak (PVL) and left ventricular outflow tract (LVOT) obstruction are frequent. METHODS: Clinical records, computer tomographic scans (CTs) and echocardiograms of consecutive MViR patients were retrospectively reviewed for anterior mitral leaflet length, CT-simulated neoLVOT, and aortomitral angle among patients with and without MViR-induced LVOT obstruction. Acute and 1-year outcomes are described. RESULTS: Twenty-two patients underwent MViR. Technical success was achieved in 13/22 (57.1%) patients, limited by paravalvular regurgitation requiring second transcatheter heart valves (THVs) in seven patients. Second valves were needed in 6/11 (54.5%) patients with 3-dimensional rings but 1/11 (9.1%, p = .06) of patients with planar rings. Procedure success at 30 days was achieved in 20/22 (90.9%) patients. There were no procedural, in-hospital, or 30-day deaths. Two patients developed significant LVOT obstruction, one managed with urgent surgery and one with elective alcohol septal ablation. Anterior mitral leaflets were longer among the two patients with LVOT obstruction than the 20 patients who did not develop LVOT obstruction when measured by TEE (30 mm vs. 21 mm, p = .009) or by CT (29 mm vs. 22 mm, p = .026). CONCLUSIONS: AML >25 mm increases the risk of MViR induced LVOT obstruction. PVL is common, particularly in 3-dimensional rings which can be managed with a second THV.

Transcatheter Aortic Valve-in-Valve Replacement for Degenerated Stentless Bioprosthetic Aortic Valves: Results of a Multicenter Retrospective Analysis.

OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) for stentless bioprosthetic aortic valves (SBAVs) and to identify predictors of adverse events. BACKGROUND: ViV TAVR in SBAVs is associated with unique technical challenges and risks. METHODS: Clinical records and computer tomographic scans were retrospectively reviewed for procedural complications, predictors of coronary obstruction, mortality, and echocardiographic results. RESULTS: Among 66 SBAV patients undergoing ViV TAVR, mortality was 2 of 66 patients (3.0%) at 30 days and 5 of 52 patients (9.6%) at 1 year. At 1 year, left ventricular end-systolic dimension was decreased versus baseline (median [interquartile range (IQR)]: 3.0 [2.6 to 3.6] cm vs. 3.7 [3.2 to 4.4] cm; p < 0.001). Coronary occlusion in 6 of 66 procedures (9.1%) resulted in myocardial infarction in 2 of 66 procedures (3.0%). Predictors of coronary occlusion included subcoronary implant technique compared with full root replacement (6 of 31, 19.4% vs. 0 of 28, 0%; p = 0.01), short simulated radial valve-to-coronary distance (median [IQR]: 3.4 [0.0 to 4.6] mm vs. 4.6 [3.2 to 6.2] mm; p = 0.016), and low coronary height (7.8 [5.8 to 10.0] mm vs. 11.6 [8.7 to 13.9] mm; p = 0.003). Coronary arteries originated <10 mm above the valve leaflets in 34 of 97 unobstructed coronary arteries (35.1%). CONCLUSIONS: TAVR in SBAVs is frequently associated with high-risk coronary anatomy but can be performed with a low risk of death and myocardial infarction, resulting in favorable ventricular remodeling. A subcoronary surgical approach is associated with an increased risk of coronary obstruction.

Novel Model to Predict Gastrointestinal Bleeding During Left Ventricular Assist Device Support.

BACKGROUND: Gastrointestinal bleeding (GIB) is a leading cause of morbidity during continuous-flow left ventricular assist device (CF-LVAD) support. GIB risk assessment could have important implications for candidate selection, informed consent, and postimplant therapeutic strategies. The aim of the study is to derive and validate a predictive model of GIB in CF-LVAD patients. METHODS AND RESULTS: CF-LVAD recipients at the Utah Transplantation Affiliated Hospitals program between 2004 and 2017 were included. GIB associated with a decrease in hemoglobin ≥2 g/dL was the primary end point. A weighted score comprising preimplant variables independently associated with GIB was derived and internally validated. A total of 351 patients (median age, 59 years; 82% male) were included. After a median of 196 days, GIB occurred in 120 (34%) patients. Independent predictors of GIB included age >54 years, history of previous bleeding, coronary artery disease, chronic kidney disease, severe right ventricular dysfunction, mean pulmonary artery pressure <18 mm Hg, and fasting glucose >107 mg/dL. A weighted score termed Utah bleeding risk score, effectively stratified patients based on their probability of GIB: low (0-1 points) 4.8%, intermediate (2-4) 39.8%, and high risk (5-9) 83.8%. Discrimination was good in the development sample (c-index: 0.83) and after internal bootstrap validation (c-index: 0.74). CONCLUSIONS: The novel Utah bleeding risk score is a simple tool that can provide personalized GIB risk estimates in CF-LVAD patients. This scoring system may assist clinicians and investigators in designing tailored risk-based strategies aimed at reducing the burden posed by GIB in the individual CF-LVAD patient and healthcare systems.

Favorable Effects on Pulmonary Vascular Hemodynamics with Continuous-Flow Left Ventricular Assist Devices Are Sustained 5 Years After Heart Transplantation.

It is unclear whether pulmonary hemodynamics improvement with left ventricle unloading with left ventricular assist devices (LVADs) is sustained long term after heart transplant (HT). We sought to assess the effects on pulmonary vascular hemodynamics during continuous-flow (CF-LVAD) and pulsatile flow (PF-LVAD) support up to 5 years after HT. Invasive hemodynamics were evaluated before LVAD, before HT, and at 3 months, 1, and 3-5 years posttransplant. Thirty-eight patients were included in the study and divided into two groups according to the type of LVAD support. The two groups were well matched in age and gender. Mean pulmonary artery pressure (PAPm) and systolic PAP (PAPs) improved significantly in the PF-LVAD group (40 ± 10.6 to 19.8 ± 4.4 mm Hg and 62.7 ± 14.9 to 31.8 ± 5.9 mm Hg, respectively) and in the CF-LVAD group (37.4 ± 11.6 to 22.4 ± 7.7 mm Hg and 53.7 ± 18.0 to 34.6 ± 11.8 mm Hg, respectively). Reductions in PAPm and PAPs were more pronounced in PF-LVAD group than in CF-LVAD group (p = 0.005 and p = 0.03, respectively). After HT, the improvement in PAPm and PAPs was sustained after 3-5 years in patients who received PF-LVAD (22.6 ± 6.5 and 32.2 ± 9.2 mm Hg, respectively) and in patients who received CF-LVAD (22.2 ± 8.4 and 33.8 ± 9.6 mm Hg, respectively). In conclusion, long-term LVAD support resulted in significant improvement in PAPm and PAPs regardless of the pump generation. The improvement in hemodynamics observed during LVAD support was sustained 3-5 years posttransplant.

Impact of Ischemic Heart Failure Etiology on Cardiac Recovery During Mechanical Unloading.

BACKGROUND: Small-scale studies focused mainly on nonischemic cardiomyopathy (NICM) have shown that a subset of left ventricular assist device (LVAD) patients can achieve significant improvement of their native heart function, but the impact of ischemic cardiomyopathy (ICM) has not been specifically investigated. Many patients with acute myocardial infarction are discharged from their index hospitalization without heart failure (HF), only to return much later with overt HF syndrome, mainly caused by chronic remodeling of the noninfarcted region of the myocardium. OBJECTIVES: This study sought to prospectively investigate the effect of ICM HF etiology on LVAD-associated improvement of cardiac structure and function using NICM as control. METHODS: Consecutive patients (n = 154) with documented chronic and dilated cardiomyopathy (ICM, n = 61; NICM, n = 93) requiring durable support with continuous-flow LVAD were prospectively evaluated with serial echocardiograms and right heart catheterizations. RESULTS: In patients supported with LVAD for at least 6 months, we found that 5% of subjects with ICM and 21% of subjects with NICM achieved left ventricular ejection fraction ≥40% (p = 0.034). LV end-diastolic and end-systolic volumes and diastolic function were significantly and similarly improved in patients with ICM and NICM. CONCLUSIONS: LVAD-associated unloading for 6 months resulted in a substantial improvement in myocardial structure, and systolic and diastolic function in 1 in 20 ICM and 1 in 5 NICM patients. These specific incidence and timeline findings may provide guidance in clinical practice and research design for sequencing and prioritizing advanced HF and heart transplantation therapeutic options in patients with ICM and NICM.

Immunologic effects of continuous-flow left ventricular assist devices before and after heart transplant.

BACKGROUND: Immune allosensitization can be triggered by continuous-flow left ventricular assist devices (CF LVAD). However, the effect of this type of allosensitization on post-transplant outcomes remains controversial. This study examined the post-transplant course in a contemporary cohort of patients undergoing transplantation with and without LVAD bridging. METHODS: We included consecutive patients who were considered for cardiac transplant from 2006 to 2015. Serum alloantibodies were detected with single-antigen beads on the Luminex platform (One Lambda Inc., Canoga Park, CA). Allosensitization was defined as calculated panel reactive antibody (cPRA) > 10%. cPRA was determined at multiple times. LVAD-associated allosensitization was defined as development of cPRA > 10% in patients with cPRA ≤ 10% before LVAD implantation. Post-transplant outcomes of interest were acute cellular rejection (ACR), antibody-mediated rejection (AMR), and survival. RESULTS: Allosensitization status was evaluated in 268 patients (20% female). Mean age was 52 ± 12 years, and 132 (49.3%) received CF LVADs. After LVAD implant, 30 patients (23%) became newly sensitized, and the level of sensitization appeared to diminish in many of these patients while awaiting transplant. During the study period, 225 of 268 patients underwent transplant, and 43 did not. A CF LVAD was used to bridge 50% of the transplant recipients. Compared with patients without new sensitization or those already sensitized at baseline, the patients with LVAD-associated sensitization had a higher risk of ACR (p = 0.049) and higher risk of AMR (p = 0.018) but a similar intermediate-term post-transplant survival. The patients who did not receive a transplant had higher level of allosensitization, with a baseline cPRA of 20% vs 6% in those who received an allograft and a high risk (40%) of death during follow-up. CONCLUSIONS: New allosensitization takes place in > 20% of patents supported with CF LVADs. Among patients who undergo transplant, this results in a higher risk of ACR and AMR, but survival remains favorable, likely due to the efficacy of current management after transplant. However, mortality in sensitized patients who do not reach transplant remains high, and new approaches are necessary to meet the needs of this group of patients.

ISHLT pathology antibody mediated rejection score correlates with increased risk of cardiovascular mortality: A retrospective validation analysis.

BACKGROUND: Antibody-mediated rejection (AMR) in cardiac transplant recipients is a serious form of rejection with adverse patient outcomes. The International Society of Heart and Lung Transplantation (ISHLT) has published a consensus schema for the pathologic diagnosis of various grades of antibody-mediated rejection (pathology antibody-mediated rejection [pAMR]). We sought to determine whether the ISHLT pAMR grading schema correlates with patient outcomes. METHODS: Using our database, which contains a semi-quantitative scoring of all pathologic descriptors of pAMR, we retrospectively used these descriptors to convert the previous AMR categories to the current ISHLT pAMR categories. Cox proportional hazard models were fit with cardiovascular (CV) death or retransplant as the outcome. The pAMR value was included as a categorical variable, and cellular rejection (CR) values were included in a separate model. RESULTS: There were 13,812 biopsies from 1,014 patients analyzed. The pAMR grades of pAMR1h, pAMR1i, and pAMR2 conferred comparable increased risk for CV mortality. Significantly increased risk of CV mortality was conferred by biopsies graded as severe AMR (pAMR3). CONCLUSIONS: The new ISHLT pAMR grading schema identifies patients at increased risk of CV mortality, consistent with risks published from several programs before 2011. The current schema is validated by this analysis in a large biopsy database. Because pAMR1h, pAMR1i, and pAMR2 have similar CV risks associated with them, the threshold for a positive diagnosis of pAMR should be re-evaluated in future iterations of the ISHLT schema.

Reasons for, and outcomes of patients who were referred for a ventricular assist device but were declined: the recent era forgotten ones.

BACKGROUND: Ventricular assist devices (VADs) have a proven survival benefit in select patients with advanced heart failure, yet many patients considered for implantation are declined for various reasons. The outcome of these patients is obscure owing to their exclusion from recent VAD studies. We aim to compare the outcomes of patients who received a VAD to those who did not. METHODS: For this study, the Artificial Heart Program's database at Intermountain Medical Center was queried from 2006 to 2012 for patients referred for a VAD. Kaplan-Meier survival analysis was performed with log-rank test determining significance. RESULTS: Of 232 patients included, 118 patients received a VAD and 114 patients did not. The prevailing reason for VAD decline in eligible and willing patients was due to pre-existing illness (39%). Mortality was higher in non-VAD vs. VAD patients (58.8% vs. 35.6%, p < 0.001) with a median time-to-death of 67 (IQR:12-314) and 301 (IQR:136-694) d, respectively (p = 0.007). CONCLUSIONS: In the current era of non-pulsatile VADs, mortality of patients who are considered but not implanted remains high. Additionally, mortality of these patients occurred much sooner. Educational efforts ensuring timely referral for VAD therapy are important to maximize the number of patients who may benefit.

Elevated resting heart rate in heart transplant recipients: innocent bystander or adverse prognostic indicator?

BACKGROUND: The elevated baseline heart rate (HR) of a heart transplant recipient has previously been considered inconsequential. However, we hypothesized that a resting HR above 100 beats per minute (bpm) may be associated with morbidity and mortality. METHODS: The U.T.A.H. Cardiac Transplant Program studied patients who received a heart transplant between 2000 and 2011. Outpatient HR values for each patient were averaged during the first year post-transplant. The study cohort was divided into two groups: the tachycardic (TC) (HR > 100 bpm) and the non-TC group (HR ≤ 100 bpm) in which mortality, incidence of rejection, and cardiac allograft vasculopathy were compared. RESULTS: Three hundred and ten patients were included as follows: 73 in the TC and 237 in the non-TC group. The TC group had a higher risk of a 10-yr all-cause mortality (p = 0.004) and cardiovascular mortality (p = 0.044). After adjustment for donor and recipient characteristics in multivariable logistic regression analysis, the hazard ratio was 3.9, (p = 0.03, CI: 1.2-13.2) and 2.6 (p = 0.02, CI: 1.2-5.5) for cardiovascular mortality and all-cause mortality, respectively. CONCLUSION: Heart transplant recipients with elevated resting HR appear to have higher mortality than those with lower resting HR. Whether pharmacologically lowering the HR would result in better outcomes warrants further investigation.

Ultraviolet Radiation Affects Thoratec HeartMate II Driveline Mechanical Properties: A Pilot Experiment.

Longevity and quality of life for left ventricular assist device (LVAD) patients are plagued by driveline exit site infections. Ultraviolet (UV) radiation, a current treatment in wound healing clinics, could potentially treat LVAD exit site infections. However, the effect of UV radiation on the tensile properties of HeartMate II (HMII) driveline material is unknown. The sleeve of a single HMII driveline was distributed into six exposure groups (n = 10/group). The six groups were further divided into two treatment cohorts designed to replicate wound treatment schedules of postimplant LVAD patients. Strip biaxial tensile tests were performed on both unexposed and exposed samples to analyze changes in material elasticity (Young's modulus), point of deformation (yield strength), and breaking point. Our data suggest that UV exposure changes the elasticity of the HMII driveline. However, the material endured aberrantly large forces and the properties remained within the safety threshold of device performance. This study warrants further examination of the effect of UV light on driveline material, to determine safety, reliability, and efficacy of UV treatment on exit site infections.

Comparing velour versus silicone interfaces at the driveline exit site of HeartMate II devices: infection rates, histopathology, and ultrastructural aspects.

BACKGROUND: Driveline exit site (DLES) infection is a major complication of ventricular assist devices (VADs). Differences in the sheath material interfacing with exit site tissue appear to affect healing time and infection risk more than site hygiene, but the mechanistic basis for this is not clear. METHODS: Health record data from Utah Artificial Heart Program patients with HeartMate II (HMII) devices implanted from 2008 to 2012 were retrospectively reviewed, with particular attention to interface type, incorporation (healing) time, and infections. Tissue samples from the DLES were collected at the time of VAD removal in a small subset. These samples were examined by routine histology and environmental scanning electron microscopy (ESEM). RESULTS: Among 57 patients with sufficient data, 15 had velour interfaces and 42 had silicone. Indications for and duration of support were similar between the groups. The silicone group had shorter incorporation time (45 ±22 vs. 56 ±34 days, P=.17) and fewer DLES infections (20% vs. 1.7%, P=.026, for patient infections and 0.0340 vs. 0.166, P=.16, for infections per patient-year). Tissues from five patients, three with velour, were examined. Velour interfaces demonstrated more hyperkeratosis, hypergranulosis, and dermal inflammation. By ESEM, the silicone driveline tracts appeared relatively smooth and flat, whereas the velour interface samples were irregular with deep fissures and globular material adhering to the surface. CONCLUSIONS: Using the silicone portion of the HMII driveline at the DLES was associated with fewer infections and a trend toward faster healing in this small retrospective series. Whether the intriguing microscopic differences directly account for this needs further study on a larger scale.

Acute on chronic pulmonary autograft dissection.

We report a case of combined acute and chronic dissection limited to the pulmonary autograft 10 years after a Ross procedure, managed by replacement with a stentless porcine bioprosthesis. Implications for timing and technique of reintervention for pulmonary autograft dilatation are discussed.

Lactic acidosis after cardiac transplantation: foe or common innocent bystander?

BACKGROUND: Lactic acidosis (LA) frequently occurs after heart transplantation (HTx). It is hypothesized to be related to inotropic support or metabolic derangements from chronic heart failure. As such, restoring hemodynamic stability with mechanical circulatory support before HTx should mitigate this problem. Our aim was to evaluate the incidence and outcomes of LA after HTx. METHODS: We evaluated HTx recipients January 2000 to May 2011. Post-HTx outcomes included graft dysfunction, length of intensive care unit stay, length of hospital stay, inotropic support, and survival. RESULTS: Of 143 eligible patients, 98.6% had LA, 67% severe, after HTx. Data were analyzed based on the severity of LA. Time to peak lactate, intensive care unit stay, length of hospital stay, peak glucose, inotropic dose, graft dysfunction, and survival after HTx were similar between groups. Statistically significant differences included pretransplant support (25.6% mechanical circulatory support in nonsevere vs. 44.9% severe LA), hospitalization at the time of HTx (37.2% vs. 21.4%), glucose at the time of peak lactate (182.88 ± 69.80 vs. 221.31 ± 56.91), ischemic time (187.4 ± 63.1 vs. 215.5 ± 68.1), and duration of inotrope. CONCLUSION: Severe LA is common after HTx, though it appears to be transient and benign. Mechanical circulatory support after HTx does not prevent LA. High lactate levels are associated with longer ischemic times, longer duration of inotrope, and correspond with higher glucose levels. The underlying mechanism is yet to be satisfactorily elucidated.

Myocardial atrophy and chronic mechanical unloading of the failing human heart: implications for cardiac assist device-induced myocardial recovery.

BACKGROUND: In animal models of heterotopic transplantation, mechanical unloading of the normal, nonhypertrophic heart results in atrophy. Primarily on the basis of these animal data, the notion that chronic left ventricular assist device (LVAD)-induced unloading will result in atrophy has dominated the clinical heart failure field, and anti-atrophic drugs have been used to enhance the cardiac recovery potential observed in some LVAD patients. However, whether unloading-induced atrophy in experimental normal heart models applies to failing and hypertrophic myocardium in heart failure patients unloaded by continuous-flow LVADs has not been studied. OBJECTIVES: The study examined whether mechanical unloading by continuous-flow LVAD leads to myocardial atrophy. METHODS: We prospectively examined myocardial tissue and hemodynamic and echocardiographic data from 44 LVAD patients and 18 untransplanted normal donors. RESULTS: Cardiomyocyte size (cross-sectional area) decreased after LVAD unloading from 1,238 ± 81 µm(2) to 1,011 ± 68 µm(2) (p = 0.001), but not beyond that of normal donor hearts (682 ± 56 µm(2)). Electron microscopy ultrastructural evaluation, cardiomyocyte glycogen content, and echocardiographic assessment of myocardial mass and left ventricular function also did not suggest myocardial atrophy. Consistent with these findings, t-tubule morphology, cytoplasmic penetration, and distance from the ryanodine receptor were not indicative of ongoing atrophic remodeling during LVAD unloading. Molecular analysis revealed no up-regulation of proatrophic genes and proteins of the ubiquitin proteasome system. CONCLUSIONS: Structural, ultrastructural, microstructural, metabolic, molecular, and clinical functional data indicated that prolonged continuous-flow LVAD unloading does not induce hypertrophy regression to the point of atrophy and degeneration. These findings may be useful in designing future investigations that combine LVAD unloading and pharmaceutical therapies as a bridge to recovery of the failing heart.

Characterization of diffuse fibrosis in the failing human heart via diffusion tensor imaging and quantitative histological validation.

Non-invasive imaging techniques are highly desirable as an alternative to conventional biopsy for the characterization of the remodeling of tissues associated with disease progression, including end-stage heart failure. Cardiac diffusion tensor imaging (DTI) has become an established method for the characterization of myocardial microstructure. However, the relationships between diffuse myocardial fibrosis, which is a key biomarker for staging and treatment planning of the failing heart, and measured DTI parameters have yet to be investigated systematically. In this study, DTI was performed on left ventricular specimens collected from patients with chronic end-stage heart failure as a result of idiopathic dilated cardiomyopathy (n = 14) and from normal donors (n = 5). Scalar DTI parameters, including fractional anisotropy (FA) and mean (MD), primary (D1 ), secondary (D2 ) and tertiary (D3 ) diffusivities, were correlated with collagen content measured by digital microscopy. Compared with hearts from normal subjects, the FA in failing hearts decreased by 22%, whereas the MD, D2 and D3 increased by 12%, 14% and 24%, respectively (P < 0.01). No significant change was detected for D1 between the two groups. Furthermore, significant correlation was observed between the DTI scalar indices and quantitative histological measurements of collagen (i.e. fibrosis). Pearson's correlation coefficients (r) between collagen content and FA, MD, D2 and D3 were -0.51, 0.59, 0.56 and 0.62 (P < 0.05), respectively. The correlation between D1 and collagen content was not significant (r = 0.46, P = 0.05). Computational modeling analysis indicated that the behaviors of the DTI parameters as a function of the degree of fibrosis were well explained by compartmental exchange between myocardial and collagenous tissues. Combined, these findings suggest that scalar DTI parameters can be used as metrics for the non-invasive assessment of diffuse fibrosis in failing hearts.

Pulsatility and the risk of nonsurgical bleeding in patients supported with the continuous-flow left ventricular assist device HeartMate II.

BACKGROUND: Bleeding is an important cause of morbidity and mortality in patients with continuous-flow left ventricular assist devices (LVADs). Reduced pulsatility has been implicated as a contributing cause. The aim of this study was to assess the effects of different degrees of pulsatility on the incidence of nonsurgical bleeding. METHODS AND RESULTS: The Utah Transplantation Affiliated Hospitals (U.T.A.H.) heart failure and transplant program databases were queried for patients with end-stage heart failure who required support with the continuous-flow LVAD HeartMate II (Thoratec Corp, Pleasanton, CA) between 2004 and 2012. Pulsatility was evaluated by means of the LVAD parameter pulsatility index (PI) and by the echocardiographic assessment of aortic valve opening during the first 3 months of LVAD support. PI was analyzed as a continuous variable and also stratified according to tertiles of all the PI measurements during the study period (low PI: <4.6, intermediate PI: 4.6-5.2, and high PI: >5.2). Major nonsurgical bleeding associated with a decrease in hemoglobin ≥2 g/dL (in the absence of hemolysis) was the primary end point. A total of 134 patients (median age of 60 [interquartile range: 49-68] years, 78% men) were included. Major bleeding occurred in 33 (25%) patients (70% gastrointestinal, 21% epistaxis, 3% genitourinary, and 6% intracranial). In multivariable analysis, PI examined either as a categorical variable, low versus high PI (hazard ratio, 4.06; 95% confidence interval, 1.35-12.21; P=0.04), or as a continuous variable (hazard ratio, 0.60; 95% confidence interval, 0.40-0.92; P=0.02) was associated with an increased risk of bleeding. CONCLUSIONS: Reduced pulsatility in patients supported with the continuous-flow LVAD HeartMate II is associated with an increased risk of nonsurgical bleeding, as evaluated by PI.

Magnitude and time course of changes induced by continuous-flow left ventricular assist device unloading in chronic heart failure: insights into cardiac recovery.

OBJECTIVES: This study sought to prospectively investigate the longitudinal effects of continuous-flow left ventricular assist device (LVAD) unloading on myocardial structure and systolic and diastolic function. BACKGROUND: The magnitude, timeline, and sustainability of changes induced by continuous-flow LVAD on the structure and function of the failing human heart are unknown. METHODS: Eighty consecutive patients with clinical characteristics consistent with chronic heart failure requiring implantation of a continuous-flow LVAD were prospectively enrolled. Serial echocardiograms (at 1, 2, 3, 4, 6, 9, and 12 months) and right heart catheterizations were performed after LVAD implant. Cardiac recovery was assessed on the basis of improvement in systolic and diastolic function indices on echocardiography that were sustained during LVAD turn-down studies. RESULTS: After 6 months of LVAD unloading, 34% of patients had a relative LV ejection fraction increase above 50% and 19% of patients, both ischemic and nonischemic, achieved an LV ejection fraction ≥ 40%. LV systolic function improved as early as 30 days, the greatest degree of improvement was achieved by 6 months of mechanical unloading and persisted over the 1-year follow up. LV diastolic function parameters also improved as early as 30 days after LVAD unloading, and this improvement persisted over time. LV end-diastolic and end-systolic volumes decreased as early as 30 days after LVAD unloading (113 vs. 77 ml/m(2), p < 0.01, and 92 vs. 60 ml/m(2), p < 0.01, respectively). LV mass decreased as early as 30 days after LVAD unloading (114 vs. 95 g/m(2), p < 0.05) and continued to do so over the 1-year follow-up but did not reach values below the normal reference range, suggesting no atrophic remodeling after prolonged LVAD unloading. CONCLUSIONS: Continuous-flow LVAD unloading induced in a subset of patients, both ischemic and nonischemic, early improvement in myocardial structure and systolic and diastolic function that was largely completed within 6 months, with no evidence of subsequent regression.