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.

Abstract 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.

Abstract 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.

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.

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/m(2) in 2.06% of patients, while 21.28%, 37.35%, and 24.97% had BMI 20-<25, 25-<30 and >= 30 kg/m(2), 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/m(2), respectively. Excessive/frequent urination was the most frequent ADR of special interest in all BMI subgroups except 20-<25 kg/m(2) (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 Conclusions Empagliflozin appeared well tolerated and effective in Japanese T2D patients regardless of BMI, although the number of patients with BMI <20 kg/m(2) was small in this study.

Lytic antibodies able to interact with the live trypomastigotes of Trypanosoma cruzi have been associated with both protection and active infection. There are T. cruzi isolates unable to induce lytic antibodies despite their capacity in eliciting agglutinins and precipitins for immunofluorescent labeling. The host's spontaneous cure was ruled out as being responsible for negative results. The test performed either at 4 C or in the presence of sodium azide proved that negative lytic assays could not be attributed to capping phenomena. The classification of the parasites as T. cruzi was confirmed by their behavior in tissue culture and in the vector, as well as by the cross-protection exhibited by chronically infected mice against other lethal T. cruzi isolates. Cross-resistance achieved by these mice also suggests that the host's protection during chronic infection is independent of the lytic antibody titer.

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. (C) 2020 by The Society of Thoracic Surgeons.

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.

With great interest, we read the article by Akay et al.,1 which concluded that higher body mass index (BMI) was associated with driveline infection (DLI) in left ventricular assist device (LVAD) patients. There has been still controversy in the association of BMI and DLI. Forest et al.2 reported similar results, which included approximately 9,000 patients from interagency registry for mechanically assisted circulatory support database. They divided patients into four groups: underweight (BMI < 18.5 kg/m2); nonobese (BMI > 18.5 to < 30 kg/m2); obese (BMI> 30 to < 40 kg/m2); and morbidly obese (BMI > 40 kg/m2), and concluded that morbidly obese was associated with ventricular assist device-related infection.2 Contrary to that, our group previously reported the relationship between lower BMI and DLI related readmission.3 Nowadays, we may better consider the limitation of BMI. Body mass index is a simple index for the evaluation of obesity, whereas it has no any other data including fat distribution, muscle volume, or metabolic disorder. The authors hypothesized that high BMI may have negative impact on the immune function and pro-inflammatory state, resulting in the development of DLI. However, the adiposity-related metabolic and immune effect may vary between central obesity and noncentral obesity,4 and the absolute value of BMI have less metabolic/nutritional information. In the current article, the No-DLI group had relatively higher white blood cell count and higher incidence of repeat sternotomy, which may result in more inflammatory condition. Further studies may be required to address the relationship between BMI and metabolic/inflammatory markers including insulin-resistance, high-sensitivity C-reactive protein, and other adipocytokines Local fat distribution may also have deep association with DLI. Some studies reported that the thickness of subcutaneous fat was associated with postoperative surgical site infection.5 The local surgical site’s thickness of subcutaneous fat may vary irrespective of the absolute value of BMI. Malnutrition may also be a significant predictor for DLI in LVAD patients. Malnutrition causes impaired immune status and an extremely thin subcutaneous tissue is vulnerable to infection from outside. In the present article, they did not analyze the DLI incidence among extremely lower BMI patients. Patients with cardiac cachexia may not be enrolled in this study. Recently some nutritional status indices were advocated as useful markers like Controlling Nutrition Status score and Prognostic Nutritional Index.6 Such markers may be more beneficial to evaluate nutritional status than just using the single value of BMI. In conclusion, the interpretation of BMI may better be with caution when considering the risk of DLI. Optimal risk stratification for future DLI and therapeutic strategy for the high-risk populations is warranted.

To the Editor: With great interest, we read the article by Akay et al.,1 which concluded that higher body mass index (BMI) was associated with driveline infection (DLI) in left ventricular assist device (LVAD) patients. There has been still controversy in the association of BMI and DLI. Forest et al.2 reported similar results, which included approximately 9,000 patients from interagency registry for mechanically assisted circulatory support database. They divided patients into four groups: underweight (BMI < 18.5 kg/m2); nonobese (BMI > 18.5 to < 30 kg/m2); obese (BMI> 30 to < 40 kg/m2); and morbidly obese (BMI > 40 kg/m2), and concluded that morbidly obese was associated with ventricular assist device-related infection.2 Contrary to that, our group previously reported the relationship between lower BMI and DLI related readmission.3 Nowadays, we may better consider the limitation of BMI. Body mass index is a simple index for the evaluation of obesity, whereas it has no any other data including fat distribution, muscle volume, or metabolic disorder. The authors hypothesized that high BMI may have negative impact on the immune function and pro-inflammatory state, resulting in the development of DLI. However, the adiposity-related metabolic and immune effect may vary between central obesity and noncentral obesity,4 and the absolute value of BMI have less metabolic/nutritional information. In the current article, the No-DLI group had relatively higher white blood cell count and higher incidence of repeat sternotomy, which may result in more inflammatory condition. Further studies may be required to address the relationship between BMI and metabolic/inflammatory markers including insulin-resistance, high-sensitivity C-reactive protein, and other adipocytokines Local fat distribution may also have deep association with DLI. Some studies reported that the thickness of subcutaneous fat was associated with postoperative surgical site infection.5 The local surgical site’s thickness of subcutaneous fat may vary irrespective of the absolute value of BMI. Malnutrition may also be a significant predictor for DLI in LVAD patients. Malnutrition causes impaired immune status and an extremely thin subcutaneous tissue is vulnerable to infection from outside. In the present article, they did not analyze the DLI incidence among extremely lower BMI patients. Patients with cardiac cachexia may not be enrolled in this study. Recently some nutritional status indices were advocated as useful markers like Controlling Nutrition Status score and Prognostic Nutritional Index.6 Such markers may be more beneficial to evaluate nutritional status than just using the single value of BMI. In conclusion, the interpretation of BMI may better be with caution when considering the risk of DLI. Optimal risk stratification for future DLI and therapeutic strategy for the high-risk populations is warranted. Daisuke NittaTeruhiko ImamuraDivision of CardiologyDepartment of MedicineThe University of Chicago MedicineChicago, Illinois

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 x (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 (R-2 = 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.

Tolvaptan is an effective therapy for heart failure patients with symptomatic congestion and hyponatremia. The efficacy of its use in patients with continuous-flow left ventricular assist devices (LVADs) is unknown. The aim of this study was to assess the clinical efficacy and safety of tolvaptan in LVAD patients. We retrospectively reviewed medical records of patients who underwent LVAD implantation between January 2014 and August 2018. Among 217 consecutive LVAD patients, tolvaptan was used in 20 patients. Mean age was 46 ± 14 years old and 14 patients were males. The duration of tolvaptan therapy was 4 (interquartile range 1-8) days. Urine volume significantly increased from 2,623 ± 1,109 ml/day before tolvaptan to 4,308 ± 1,432 ml/day during tolvaptan therapy (p < 0.001). Serum sodium increased from 127 ± 3 to 133 ± 3 mEq/L at the end of tolvaptan therapy (p < 0.001). No patients developed hypernatremia (serum sodium >150 mEq/L). The 90-day overall survival following tolvaptan therapy was 89% in both the tolvaptan group and a propensity score-matched non-tolvaptan group (p = 0.918). Survival free of heart failure readmissions was also comparable between the groups (p = 0.751). In conclusion, short-term use of tolvaptan following LVAD implantation is a safe and effective therapy to augment diuresis and improve hyponatremia.

Abstract 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.

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 ± 29.0 and 61.6 ± 23.8 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 ± 3.4 [with fatigue] vs 17.4 ± 4.7 [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.

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.

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.

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.

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.

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.

Although a correlation between the nutritional status and the prognosis of patients with heart failure has been suggested, a correlation between the nutritional status and outcomes after the left ventricular assist device (LVAD) implantation remains unclear. We aimed to investigate the efficacy of the Controlling Nutritional Status (CONUT) score (range 0–12, including serum albumin, total cholesterol, and lymphocytes) as a nutritional index in speculating the prognosis of patients undergoing LVAD implantation. We examined 63 consecutive patients who underwent the continuous-flow LVAD implantation. Using the preoperative CONUT score, patients were categorized into two groups: lower CONUT score (0–4: normal to mild malnutrition) and higher CONUT score (5–12: moderate to severe malnutrition). We compared for the backgrounds and the clinical events after LVAD implantation. The higher CONUT group exhibited a significantly higher mean right atrial pressure (10.9 ± 4.7 vs. 7.3 ± 4.1 mmHg; p = 0.0019). In that group, the mortality rate was significantly higher (25% vs. 2.6%; p = 0.0059) and the Kaplan–Meier analysis showed lower survival rate. Furthermore, more bleeding events significantly occurred in the higher CONUT group. The preoperative CONUT score may reflect systemic venous congestion and offer a useful prognostic index of clinical courses after LVAD implantation.