Empagliflozin cost-effectiveness analysis in Japanese heart failure with mildly reduced and preserved ejection fraction.

AIMS: Empagliflozin, a sodium-glucose co-transporter 2 inhibitor, was shown to be effective in patients with heart failure with preserved ejection fraction (HFpEF) in the EMPEROR-Preserved trial. The present study aims to evaluate the cost-effectiveness of empagliflozin among Japanese patients with HFpEF. METHODS AND RESULTS: A Markov cohort model was developed to evaluate the cost-effectiveness of empagliflozin added to standard of care (SoC) compared with SoC alone in patients with HFpEF from the perspective of the Japanese healthcare system and with a lifetime horizon. In addition to clinical events, the progression of disease severity was modelled based on the migration of Kansas City Cardiomyopathy Questionnaire-Clinical Summary Scores (KCCQ-CSS). Model inputs, including risk of clinical events, costs, and utilities/disutilities, were derived from EMPEROR-Preserved trial data, a claims database and published literature. The generalizability of model results was investigated by applying various subgroups including age, body mass index (BMI), and region Asia, based on the subgroup analysis of EMPEROR-Preserved data. In the base-case analysis, empagliflozin yielded additional quality-adjusted life years (QALYs; 0.11) with an incremental cost of $1408 per patient for Japanese patients with HFpEF. Incremental cost, mainly derived from drug acquisition cost ($1963 per patient), was largely offset by reduced cost in hospitalization for heart failure (HHF) and cardiovascular death (-$537 per patient and -$166 per patient, respectively). Treatment of empagliflozin provided incremental 0.11 QALYs and 0.08 life years compared with SoC alone. The incremental cost-effectiveness ratio (ICER) was $12 772 (¥1 662 689)/QALY, which was below the Japanese willingness-to-pay (WTP) threshold of $38 408 (¥5 000 000)/QALY. The results were consistent across all the subgroups considered, and empagliflozin was dominant over SoC alone in the region Asia and BMI < 25 kg/m2 subgroups. ICERs for the remaining subgroups ranged from $7520/QALY (¥978 972/QALY, patients with baseline age ≥ 75 years) to $31 049/QALY (¥4 041 896/QALY, patients with baseline New York Heart Association class III/IV). Deterministic sensitivity analysis result showed that the treatment effect on HHF is the biggest driver of the cost-effectiveness analysis, while the ICER will be still under the threshold even if no effect of empagliflozin on HHF was assumed. The probabilistic sensitivity analysis result showed that 64% of simulations were cost-effective based on the Japanese WTP threshold. CONCLUSIONS: Empagliflozin was demonstrated to be cost-effective for patients with HFpEF in Japan based on EMPEROR-Preserved trial data.

Efficacy of empagliflozin in heart failure with preserved ejection fraction according to frailty status in EMPEROR-Preserved.

BACKGROUND: Frailty is a severe, common co-morbidity associated with heart failure (HF) with preserved ejection fraction (HFpEF). The impact of frailty on HFpEF outcomes may affect treatment choices in HFpEF. The impact of frailty on HFpEF patients and any impact on the clinical benefits of sodium glucose co-transporter 2 (SGLT2) inhibition in HFpEF have been described in only a limited number of trials. Whether the SGLT2 inhibitor empagliflozin would improve or worsen frailty status when given to HFpEF patients is also not known. The aims of this study were, therefore, to evaluate, in HFpEF patients enrolled in the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), the impact of frailty on clinical outcomes, and on the effects of empagliflozin, as well as the effect of empagliflozin on frailty status during treatment period. METHODS: We calculated a cumulative deficit-derived frailty index (FI) using 44 variables including clinical, laboratory and quality of life parameters recorded in EMPEROR-Preserved. Patients were classified into four groups: non-frail (FI < 0.21), mild frailty (0.21 to <0.30), moderate frailty (0.30 to <0.40) and severe frailty (≥0.40). Clinical outcomes and health-related quality of life were evaluated according to baseline FI along with the effect of empagliflozin on chronological changes in FI (at 12, 32 and 52 weeks). RESULTS: The patient distribution was 1514 (25.3%), 2100 (35.1%), 1501 (25.1%) and 873 (14.6%) in non-frail, mild frailty, moderate frailty and severe frailty, respectively. Severe frailty patients tended to be female and have low Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, more co-morbidities and more polypharmacy. Incidence rates of the primary outcome of cardiovascular death or HF hospitalization increased as frailty worsened (hazard ratio [HR] of each FI category compared with the non-frail group: 1.10 [95% confidence interval, CI, 0.89-1.35], 2.00 [1.63-2.47] and 2.61 [2.08-3.27] in the mild frailty, moderate frailty and severe frailty groups, respectively; P trend < 0.001). Compared with placebo, empagliflozin reduced the risk for the primary outcome across the four FI categories, HR: 0.59 [95% CI 0.42-0.83], 0.79 [0.61-1.01], 0.77 [0.61-0.96] and 0.90 [0.69-1.16] in non-frail to severe frailty categories, respectively (P value for trend = 0.097). Empagliflozin also improved other clinical outcomes and KCCQ score across frailty categories. Compared with placebo, empagliflozin-treated patients had a higher likelihood of being in a lower FI category at Weeks 12, 32 and 52 (P < 0.05), odds ratio: 1.12 [95% CI 1.01-1.24] at Week 12, 1.21 [1.09-1.34] at Week 32 and 1.20 [1.09-1.33] at Week 52. CONCLUSIONS: Empagliflozin improved key efficacy outcomes with a possible diminution of effect in very frail patients. Empagliflozin also improved frailty status during follow-up.

Cost-effectiveness analysis of empagliflozin in patients with heart failure with reduced ejection fraction in Japan based on the EMPEROR-Reduced trial.

BACKGROUND: Several studies have reported the cost-effectiveness of sodium-glucose co-transporter 2 inhibitors in heart failure patients; however, their economic implications have not been sufficiently elucidated in Japan. METHODS: A Markov cohort model was developed to evaluate the cost-effectiveness of empagliflozin plus standard of care (SoC) vs. SoC for patients with heart failure with reduced ejection fraction (HFrEF) in Japan. Model inputs, including risk of clinical events, costs, and utilities based on Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores were derived from EMPEROR-Reduced trial data, published literature, and a claims database. RESULTS: The model predicted lower lifetime hospitalizations for heart failure (HHFs) and additional quality-adjusted life-years (QALYs; 0.21) for empagliflozin plus SoC vs. SoC in the overall population. Increased costs of ¥100,495/patient ($772/patient), primarily driven by higher drug costs of ¥239,558/patient ($1,840/patient), were largely offset by reduced HHF management costs of -¥166,160/patient (-$1,276/patient), yielding an incremental cost-effectiveness ratio (ICER) of ¥469,672/QALY ($3,608/QALY). Results were consistent among subgroups and sensitivity analyses. In probabilistic sensitivity analysis, 82.5 % of runs were below the Japanese ICER reference value of ¥5,000,000/QALY ($38,408/QALY). CONCLUSIONS: Empagliflozin was demonstrated to be cost-effective for HFrEF patients in Japan based on the EMPEROR-Reduced trial data.

Early treatment with a sodium-glucose co-transporter 2 inhibitor in high-risk patients with acute heart failure: Rationale for and design of the EMPA-AHF trial.

AIMS: The aim of the EMPA-AHF trial is to clarify whether early initiation of a sodium-glucose co-transporter 2 inhibitor before clinical stabilization is safe and beneficial for patients with acute heart failure (AHF) who are at a high risk of adverse events. METHODS: The EMPA-AHF trial is a randomized, double-blind, placebo-controlled, multicentre trial examining the efficacy and safety of early initiation of empagliflozin (10 mg once daily). In total, 500 patients admitted for AHF will be randomized 1:1 to either empagliflozin 10 mg daily or placebo at 47 sites in Japan. Study entry requires hospitalization for AHF with dyspnoea, signs of volume overload, elevated natriuretic peptide, and at least one of the following criteria: estimated glomerular filtration rate <60 mL/min/1.73 m2; already taking ≥40 mg of furosemide daily before hospitalization; and urine output of <300 mL within 2 hours after an adequate dose of intravenous furosemide. Patients will be randomized within 12 hours of hospital presentation, with treatment continued up to 90 days. The primary outcome is the clinical benefit of empagliflozin on the win ratio for a hierarchical composite endpoint consisting of death within 90 days, heart failure rehospitalization within 90 days, worsening heart failure during hospitalization, and urine output within 48 hours after treatment initiation. CONCLUSION: The EMPA-AHF trial is the first to evaluate the efficacy and safety of early initiation of empagliflozin in patients with AHF considered to be at high risk under conventional treatment.

Safety and effectiveness of empagliflozin and linagliptin fixed-dose combination therapy in Japanese patients with type 2 diabetes: final results of a one-year post-marketing surveillance study.

BACKGROUND: Fixed-dose combination (FDC) of the sodium-glucose co-transporter 2 inhibitor empagliflozin and the dipeptidyl peptidase-4 inhibitor linagliptin was approved for type 2 diabetes (T2D) treatment in Japan in 2018. We conducted a post-marketing surveillance study of empagliflozin/linagliptin FDC in routine clinical practice in Japan. RESEARCH DESIGN AND METHODS: This one-year, prospective, multicenter, observational study investigated the safety and effectiveness of empagliflozin/linagliptin FDC in Japanese patients with T2D. The primary outcome was incidence of adverse drug reactions (ADRs). RESULTS: Among 1146 patients, mean (SD) age was 63.8 (12.8) years and 22.08% were aged ≥75 years. Mean (SD) glycated hemoglobin (HbA1c) was 7.66% (1.21); fasting plasma glucose (FPG) was 142.90 mg/dl (43.75). ADRs were experienced by 32 (2.79%) patients (1 serious ADR); ADRs of important identified risk included urinary tract infection (7 patients [0.61%]), hypoglycemia (2 [0.17%]), ketoacidosis (0), genital infection (1 [0.09%]), and volume depletion (1 [0.09%]). Overall mean (SD) change from baseline in body weight, HbA1c, and FPG were -1.08 kg (3.21), -0.39% (1.11), and -7.90 mg/dl (39.12), respectively. CONCLUSIONS: Empagliflozin/linagliptin FDC was effective and generally well tolerated in Japanese patients with T2D; no new safety concerns were identified. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT03761797) [Figure: see text] [Figure: see text].

Safety and effectiveness of empagliflozin according to body mass index in Japanese patients with type 2 diabetes: a subgroup analysis of a 3-year post-marketing surveillance study.

BACKGROUND: Empagliflozin, a glucose-lowering drug licensed for type 2 diabetes (T2D), demonstrated tolerability and effectiveness overall in a post-marketing surveillance (PMS) study in Japan. However, the impact of body mass index (BMI) is unclear. RESEARCH DESIGN AND METHODS: This was a prespecified sub-analysis of the prospective, 3-year, PMS study of empagliflozin in Japan where the primary endpoint was adverse drug reactions (ADRs). We evaluated results according to BMI. RESULTS: We enrolled 7931 T2D patients treated with empagliflozin. Baseline mean age was 58.7 years; 63.01% were male. Baseline BMI was <20 kg/m2 in 2.06% of patients, while 21.28%, 37.35%, and 24.97% had BMI 20-<25, 25-<30 and ≥30 kg/m2, respectively. ADRs occurred in 19 (11.66%), 203 (12.03%), 411 (13.88%), and 295 (14.90%) patients with BMI <20, 20-<25, 25-<30 and ≥30 kg/m2, respectively. Excessive/frequent urination was the most frequent ADR of special interest in all BMI subgroups except 20-<25 kg/m2 (urinary tract infection). Mean change in glycated hemoglobin from baseline was -0.75%, with similar magnitude across BMI subgroups. Body-weight reduction seemed dependent on BMI, with almost no change in the <20 kg/m2 subgroup. CONCLUSIONS: Empagliflozin appeared well tolerated and effective in Japanese T2D patients regardless of BMI, although the number of patients with BMI <20 kg/m2 was small in this study.

Impact of worsening of aortic insufficiency during HeartMate 3 LVAD support.

Aortic insufficiency remains a difficult to treat and highly morbid condition even in the era of HeartMate 3 left ventricular assist devices (LVADs). The prognostic nature of the longitudinal progression of aortic insufficiency, however, remains unknown. We prospectively collected data on patients who received HeartMate 3 LVAD implantation, who had assessments of aortic insufficiency using a novel Doppler echocardiography obtained at outflow graft at three (baseline) and 6 months postimplant. Patients with moderate or greater aortic insufficiency at baseline were excluded. The risk of aortic insufficiency progression on 1-year death and readmission for heart failure was investigated. In total, 41 patients (median 51 years old and 29 males) were included. All patients had less than moderate aortic insufficiency at baseline. Of them, 22 patients had worsening aortic insufficiency for 3 months following baseline assessments, which was associated with a significantly higher risk of 1-year death or heart failure readmission rate (41% vs. 11%, P = .023) with a hazard ratio of 3.24 (95% confidence interval 1.02-18.5, P = .038) adjusted for device speed at baseline and destination therapy indication. In patients with HeartMate 3 LVADs, progressive aortic insufficiency may be associated with a higher risk of 1-year death or readmission for heart failure. Close monitoring of patients with baseline aortic insufficiency should be considered as a measure to risk-stratify those for future adverse events.

Hypogammaglobulinemia following heart transplantation: Prevalence, predictors, and clinical importance.

Hypogammaglobulinemia (HGG) can occur following solid organ transplantation. However, there are limited data describing the prevalence, risk factors, and clinical outcomes associated with HGG following heart transplantation. We retrospectively reviewed data of 132 patients who had undergone heart transplantation at our institution between April 2014 and December 2018. We classified patients into three groups based on the lowest serum IgG level post-transplant: normal (≥700 mg/dL), mild HGG (≥450 and <700 mg/dL), and severe HGG (<450 mg/dL). We compared clinical outcomes from the date of the lowest IgG level. Mean age was 57 (47, 64) years, and 94 (71%) patients were male. Prevalence of severe HGG was the highest (27%) at 3-6 months following heart transplantation and then decreased to 5% after 1 year. Multivariate analysis showed that older age and Caucasian race were independent risk factors for HGG. Overall survival was comparable between the groups; however, survival free of infection was 73%, 60%, and 45% at 1 year in the normal, mild HGG, and severe HGG groups, respectively (P = .013). In conclusion, there is a high prevalence of HGG in the early post-heart transplant period that decreases over time. HGG is associated with an increased incidence of infection.

Clinical importance of respiratory muscle fatigue in patients with cardiovascular disease.

Patients with cardiovascular diseases frequently experience exertional dyspnea. However, the relationship between respiratory muscle strength including its fatigue and cardiovascular dysfunctions remains to be clarified.The maximal inspiratory pressure/maximal expiratory pressure (MIP/MEP) before and after cardiopulmonary exercise testing (CPX) in 44 patients with heart failure and ischemic heart disease were measured. Respiratory muscle fatigue was evaluated by calculating MIP (MIPpost/MIPpre) and MEP (MEPpost/MEPpre) changes.The mean MIPpre and MEPpre values were 67.5 ±â€Š29.0 and 61.6 ±â€Š23.8 cm H2O, respectively. After CPX, MIP decreased in 25 patients, and MEP decreased in 22 patients. We evaluated the correlation relationship between respiratory muscle function including respiratory muscle fatigue and exercise capacity evaluated by CPX such as peak VO2 and VE/VCO2 slope. Among MIP, MEP, change in MIP, and change in MEP, only the value of change in MIP had an association with the value of VE/VCO2 slope (R = -0.36, P = .017). In addition, multivariate analysis for determining factor of change in MIP revealed that the association between the change in MIP and eGFR was independent from other confounding parameters (beta, 0.40, P = .017). The patients were divided into 2 groups, with (MIP change < 0.9) and without respiratory muscle fatigue (MIP change > 0.9), and a significant difference in peak VO2 (14.2 ±â€Š3.4 [with fatigue] vs 17.4 ±â€Š4.7 [without fatigue] mL/kg/min; P = .020) was observed between the groups.Respiratory muscle fatigue demonstrated by the change of MIP before and after CPX significantly correlated with exercise capacity and renal function in patients with cardiovascular disease.

Optimal cannula positioning of HeartMate 3 left ventricular assist device.

Cannula position in HeartMate II and HeartWare left ventricular assist devices (LVADs) is associated with clinical outcome. This study aimed to investigate the clinical implication of the device positioning in HeartMate 3 LVAD cohort. Consecutive patients who underwent HeartMate 3 LVAD implantation were followed for one year from index discharge. At index discharge, chest X-ray parameters were measured: (a) cannula coronal angle, (b) height of pump bottom, (c) cannula sagittal angle, and (d) cannula lumen area. The association of each measurement of cannula position with one-year clinical outcomes was investigated. Sixty-four HeartMate 3 LVAD patients (58 years old, 64% male) were enrolled. In the multivariable Cox regression model, the cannula coronal angle was a significant predictor of death or heart failure readmission (hazard ratio 1.27 [1.01-1.60], P = .045). Patients with a cannula coronal angle ≤28° had lower central venous pressure (P = .030), lower pulmonary capillary wedge pressure (P = .027), and smaller left ventricular size (P = .019) compared to those with the angle >28°. Right ventricular size and parameters of right ventricular function were also better in the narrow angle group, as was one-year cumulative incidence of death or heart failure readmission (10% vs. 50%, P = .008). Narrow cannula coronal angle in patients with HeartMate 3 LVADs was associated with improved cardiac unloading and lower incidence of death or heart failure readmission. Larger studies to confirm the implication of optimal device positioning are warranted.

Aortic Insufficiency During HeartMate 3 Left Ventricular Assist Device Support.

BACKGROUND: Aortic insufficiency (AI) is associated with morbidity and mortality in patients with continuous-flow left ventricular assist devices (LVADs), whereas its impact on the HeartMate 3 LVAD cohorts remains uninvestigated. We aimed to investigate the clinical impact of AI on patients with HeartMate 3 LVADs. METHODS AND RESULTS: Consecutive 61 patients (median age 54 years; 67% male) implanted with HeartMate 3 LVAD between 2015 and 2019 were enrolled and underwent echocardiography at 3 months after LVAD implantation. AI severity was quantified by the novel Doppler echocardiographic method obtained at the outflow cannula and the calculated regurgitation fraction of 30% or greater (moderate or greater) was defined as significant. At 3 months after implant, 12 patients (20%) had significant AI. They had a higher incidence of death or heart failure readmissions compared with those without significant AI during a 1-year observational period (70% vs 24%, P = .003) with an adjusted hazard ratio of 2.76 (95% confidence interval 1.03-7.88). CONCLUSIONS: In patients with HeartMate 3 LVAD support, significant AI remains both prevalent and a clinically significant downstream complication.

Impact of tacrolimus versus cyclosporin A on renal function during the first year after heart transplant.

AIMS: Nephrotoxicity of calcineurin inhibitors (CNIs) is associated with adverse events in patients undergoing heart transplant (HTx), although studies directly comparing tacrolimus (TAC) versus cyclosporin A (CsA), especially in combination with everolimus and low-dose CNIs approach, are limited. Thus, we sought to investigate the associations of TAC and CsA with clinical outcomes in HTx recipients, with specific focus on renal function. METHODS AND RESULTS: From August 2007 to February 2017, 72 consecutive patients (39 treated with TAC vs. 33 with CsA) receiving de novo HTx in a single transplant centre were retrospectively evaluated. We used the instrumental variable method to account for unmeasured confounding. The study outcomes were percentage change in estimated glomerular filtration rates (eGFR) (safety endpoint) and biopsy-proven acute rejection (efficacy endpoint) within the first year after HTx. The enrolled patients (median age 40 years) were predominantly men (68%). There were no significant differences in baseline characteristics, including eGFR (64.8 [45.7-96.4] mL/min/1.73 m2 in TAC vs. 65.6 [57.9-83.0] mL/min/1.73 m2 for CsA; P = 0.48), other than sex (male, 49% for TAC vs. 91% for CsA; P < 0.001) between the two groups. Within the first year after HTx, 23 (59%) in the TAC group switched mycophenolate mofetil to everolimus, whereas 16 (48%) in the CsA group (P = 0.52). At 12 months, the rates of mortality and end-stage renal disease requiring renal replacement therapies were both 0%. In the instrumental variable analysis, no differences in renal function as well as graft rejection for 1 year after HTx existed between the TAC and CsA groups. These results were similar when taking into account of everolimus use. CONCLUSIONS: Irrespective of everolimus use with low-dose CNIs, our analysis using the instrumental variable method showed no differences in renal function as well as graft rejection during the first year after HTx between HTx recipients who received TAC or CsA.

Longitudinal Trajectories of Hemodynamics Following Left Ventricular Assist Device Implantation.

BACKGROUND: Continuous-flow left ventricular assist devices (LVADs) improve the hemodynamics of patients with advanced heart failure. However, the longitudinal trajectories of hemodynamics in patients after LVAD implantation remain unknown. The aim of this study was to investigate the trends of hemodynamic parameters following LVAD implantation. METHODS AND RESULTS: We retrospectively reviewed patients who underwent LVAD implantation between April 2014 and August 2018. We collected hemodynamic parameters from right heart catheterizations. Of 199 consecutive patients, we enrolled 150 patients who had both pre- and postimplant right heart catheterizations. They had 3 (2, 4) postimplant right heart catheterizations during a follow-up of 2.3 (1.3, 3.1) years. The mean age was 57 ± 13 years, and 102 patients (68%) were male. Following LVAD implantation, pulmonary arterial pressure and pulmonary capillary wedge pressure decreased, and cardiac index increased significantly, then remained unchanged throughout follow-up. Right atrial pressure decreased initially and then gradually increased to preimplant values. The pulmonary artery pulsatility index decreased initially and returned to preimplant values, then progressively decreased over longer follow-up. Subgroup analysis showed significant differences in the trajectories of the pulmonary artery pulsatility index based on gender. CONCLUSIONS: Despite improvement in left-side filling pressures and cardiac index following LVAD implantation, right atrial pressure increased and the pulmonary artery pulsatility index decreased over time, suggesting progressive right ventricular dysfunction.

HeartWare Ventricular Assist Device Cannula Position and Hemocompatibility-Related Adverse Events.

BACKGROUND: HeartWare ventricular assist device (HVAD) cannula position is associated with hemodynamics and heart failure readmissions. However, its impact on hemocompatibility-related adverse events (HRAEs) remains uncertain. METHODS: HVAD patients were followed for 1 year after index hospitalization, when cannula coronal angle was quantified from chest x-ray film. Invasive right heart catheterization and transthoracic echocardiography were performed. One-year occurrences of each HRAE were compared between those with and without a cannula coronal angle of greater than 65 degrees. RESULTS: Among 63 HVAD patients (median age 60 years, 63% male), 10 (16%) had a cannula coronal angle greater than 65 degrees. The wide-angle group had elevated intracardiac pressures and lower pulmonary artery pulsatility index (P < .05). They also had reduced right ventricular function by echocardiography. Freedom from HRAEs tended to be lower in the wide-angle group (24% vs 62%; P = .11). The rate of gastrointestinal bleeding was significantly higher in the greater than 65 degrees group (0.90 events/year vs 0.40 events/year; P = .013). The rates of stroke and pump thrombosis were statistically comparable irrespective of cannula angle (P > .05). CONCLUSIONS: HVAD cannula coronal angle was associated with reduced right ventricular function and HRAEs. Prospective studies evaluating surgical techniques to ensure optimal device positioning and its effects on HRAEs are warranted.

Effect of Concomitant Tricuspid Valve Surgery With Left Ventricular Assist Device Implantation.

BACKGROUND: Tricuspid regurgitation (TR) is common in advanced heart failure (HF) patients. However, the effect of concomitant tricuspid valve repair or replacement (tricuspid valve intervention [TVI]) with left ventricular assist device (LVAD) implantation is controversial. The aim of this study was to investigate the longitudinal trend of TR after LVAD implantation and the effect of TVI on the TR trend and clinical outcomes. METHODS: We retrospectively reviewed patients at our institution who underwent LVAD implantation between April 2014 and August 2018. We evaluated the grade of TR by echocardiography before and after LVAD implantation. Moderate or greater TR was defined as significant. RESULTS: Among 199 consecutive patients, 194 had at least 2 echocardiographic TR assessments before and after LVAD implantation. Of these patients, 108 were included in the TVI-positive (TVI+) group and 86 in the TVI-negative (TVI-) group. In the TVI+ group, the prevalence of significant TR decreased from 52% to about 20% in the first 6 months after implantation (P < .01). Overall survival and HF readmission-free survival were comparable between the TVI+ and TVI- patients. In contrast, patients in both groups who had significant postoperative TR during early follow-up had worse 2-year HF readmission-free survival (36% in patients with significant postoperative TR vs 55% in those without significant postoperative TR; P = .028). CONCLUSIONS: Concomitant TVI with LVAD implantation improved TR in most patients but did not have an impact on clinical outcomes. Significant postoperative TR after LVAD implantation, in patients with and without TVI, was associated with worse HF-free outcomes.

Deep Y-Descent in Right Atrial Waveforms Following Left Ventricular Assist Device Implantation.

BACKGROUND: Characterization of right heart catheterization (RHC) waveforms provides diagnostic and clinical information in heart failure patients. We aimed to investigate the implication of RHC waveforms, specifically the y-descent, in patients with left ventricular assist device (LVAD). METHODS AND RESULTS: Patients underwent RHC and waveforms were quantified prior to and 6 months after LVAD implantation. The impact of a deep y-descent (>3 mmHg) on echocardiographic measures of right heart function and 1-year hemocompatibility-related adverse event rates were investigated. Eighty-nine patients (median 59 years old, 65 male) underwent RHC. RHC waveform showed unique changes following LVAD implantation, particularly an increase in the steepness of the y-descent. A post-LVAD deep y-descent was associated with reduced right ventricular function and enlarged right heart. Patients with post-LVAD deep y-descent had higher rates of gastrointestinal bleeding (0.866 vs 0.191 events/year) and stroke (0.199 vs 0 events/year) compared with those without (P< .05 for both). CONCLUSION: RHC waveforms characterized by deep y-descent on RHC waveform during LVAD support was associated with impaired right ventricular function and worse clinical outcomes.

HVAD Flow Waveform Estimates Left Ventricular Filling Pressure.

BACKGROUND: HVAD left ventricular assist device flow waveforms provides graphical real-time information linking device performance with invasive hemodynamics. Previous studies have demonstrated a good correlation between the slopes of the ventricular filling phase slope (VFPS) and directly measured pulmonary capillary wedge pressure (PCWP). We aimed to validate the utility of VFPS to estimate PCWP and predict clinical outcomes. METHODS: In this prospective blinded study, screenshots from the HVAD monitor and simultaneous invasive hemodynamic measurements were obtained. Each screenshot was digitized and the VFPS was calculated by 2 independent reviewers who were blinded to the hemodynamic results. The equation PCWP = 7.053 +1.365 × (VFPS) was derived from a previously published dataset and the estimated PCWP was correlated to the actually measured PCWP. RESULTS: One hundred thirty-one sets of simultaneous measurements (VFPS and PCWP) were obtained from 27 HVAD patients (mean age 55 years, 47% male). A previously proposed cutoff of VFPS ≥5.8 L/min/s predicted PCWP ≥ 18 mmHg with 91.5% sensitivity and 95.2% specificity with the area under curve of 0.987. The estimated PCWP significantly correlated with measured PCWP (R2 = 0.65, P < .001) and showed acceptable agreement with measured PCWP. Patients with VFPS ≥ 5.8 L/min/s experienced significantly higher heart failure readmission rates than those without (0.24 vs 0.05 events/y, P < .001). CONCLUSIONS: VFPS of the HVAD flow waveform is a novel noninvasive parameter that can estimate PCWP.

Estimation of the Severity of Aortic Insufficiency by HVAD Flow Waveform.

PURPOSE: Aortic insufficiency (AI) significantly affects morbidity and mortality in patients with left ventricular assist devices. Although AI may be commonly assessed by echocardiography, expert techniques are required for accurate quantification of AI severity. DESCRIPTION: In this prospective blinded study, screenshots from the HVAD (Medtronic, Framingham, MA) display and simultaneous echocardiographic measurements were obtained. Each screenshot was digitized and the early diastolic phase slope was calculated, with blinding to the echocardiographic results. The regurgitant fraction of AI was quantified by Doppler echocardiography of the outflow graft. EVALUATION: A total of 30 patients (median, 57 years old; 57% male) were enrolled. A cutoff of -17.6 L/min/s for the early diastolic phase slope had a sensitivity of 0.92 and a specificity of 0.53 to estimate significant AI with a regurgitant fraction of 30% or greater, and it significantly stratified patients into a low regurgitant faction group (0.3%) and a high regurgitant fraction group (33.0%) (P = .009). The early diastolic phase slope had a moderate correlation with the actually measured regurgitant fraction (r = .50). CONCLUSIONS: The early diastolic phase slope of the HVAD flow waveform may be a parameter that can estimate the presence of clinically significant AI.

Significant impact of left ventricular assist device models on the value of flow-mediated dilation: effects of LVAD on endothelial function.

The precise physiological changes associated with the use of left ventricular assist device (LVAD) are not well characterized. We examined the impact of changes in hemodynamic state using LVAD on endothelial function. We measured flow-mediated vasodilation (FMD) to evaluate endothelial vasodilator function of the brachial artery in 53 patients (dilated cardiomyopathy: 39, ischemic cardiomyopathy: 4, and others: 10) with an implanted LVAD (DuraHeart, EVAHEART, or HeartMate II). We found that FMD value in the HeartMateII LVAD group (9.3% ± 2.9%) was significantly higher than those in the other two groups (EVAHEART: 6.7% ± 2.8% and DuraHeart: 6.2% ± 4.0%). Other factors that affected the FMD value were age (r = - 0.31, p = 0.026), Brinkman index (r = - 0.30, p = 0.029); however, aortic opening, aortic regurgitation, and other hemodynamic parameters such as cardiac index or pulmonary capillary wedge pressure did not correlate with FMD. Multivariate analyses revealed that the difference among the LVAD models most significantly affected the FMD values after adjusting for age and smoking status (t = 2.6, p = 0.014). Event free survival rate of death and cerebral infarction was not significantly different according to the value of FMD. The difference among the LVAD groups most significantly affected the state of endothelial function and it had more impact than other clinical factors.