New-Onset Neurosarcoidosis Following Heart Transplant for Cardiac Sarcoidosis.

A 63-year-old woman who underwent heart transplantation for cardiac sarcoidosis developed new headache and vision changes. Extensive workup resulted in a diagnosis of neurosarcoidosis treated with pulse dose steroids and infliximab. Recurrence of sarcoidosis after transplantation for isolated cardiac sarcoidosis occurs, but optimal surveillance methods remain unknown.

The Seattle Heart Failure Model in Kidney Transplant Recipients.

Cardiovascular disease is the leading cause of mortality following kidney transplantation. Heart failure affects 17-21% of patients with chronic kidney disease and increases along with time receiving dialysis. The Seattle Heart Failure Model (SHFM) is a validated mortality risk model for heart failure patients that incorporates clinical, therapeutic, and laboratory parameters but does not include measures of kidney function. We applied the SHFM to patients with end-stage renal disease (ESRD) who were being evaluated for kidney transplantation to determine if the model was associated with post-transplant mortality. This retrospective single-center study analyzed survival among 360 adult deceased-donor kidney transplant recipients. Cox regression was used to model post-transplant patient survival. Our findings indicated that a 1.0-point increase in the adapted SHFM score was significantly associated with post-transplant mortality (HR 1.76, 95% CI = 1.10-2.83, p = 0.02), independently of the Kidney Donor Profile Index and Estimated Post-Transplant Survival. Individual covariates of the SHFM were evaluated in univariate analyses, and age, sodium, cholesterol, and lymphocyte count were significantly related to mortality. This study provides preliminary evidence that an adapted SHFM score could be a useful tool in evaluating mortality risk post-transplant in patients with ESRD.

The prognostic role of advanced hemodynamic variables in patients with left ventricular assist devices.

BACKGROUND: Invasive hemodynamic variables obtained from right heart catheterization have been used for risk-stratifying patients with advanced heart failure (HF). However, there is a paucity of data on the prognostic value of invasive hemodynamic variables in patients with left ventricular assist devices (LVAD). We hypothesized that cardiac power output (CPO), cardiac power efficiency (CPE), and left ventricular stroke work index (LVSWI) can serve as prognostic markers in patients with LVADs. METHODS: Baseline hemodynamic data from patients who had LVAD ramp studies at our institution from 4/2014 to 7/2018 were prospectively collected, from which advanced hemodynamic variables (CPO, CPE, and LVSWI) were retrospectively analyzed. Univariate and multivariable analyses were performed for hemocompatibility-related adverse events (HRAE), HF admissions, and mortality. RESULTS: Ninety-one participants (age 61 ± 11 years, 34% women, 40% Black or African American, and 38% ischemic cardiomyopathy) were analyzed. Low CPE was significantly associated with mortality (HR 2.42, 95% CI 1.02-5.74, p = 0.045) in univariate analysis and Kaplan-Meier analysis (p = 0.04). Low LVSWI was significantly associated with mortality (HR 2.13, 95% CI 1.09-4.17, p = 0.03) in univariate analysis and Kaplan-Meier analysis (p = 0.02). CPO was not associated with mortality. CPO, CPE, and LVSWI were not associated with HRAE or HF admissions. CONCLUSIONS: Advanced hemodynamic variables can serve as prognostic indicators for patients with LVADs. Low CPE and LVSWI are prognostic for higher mortality, but no variables were associated with HF admissions or HRAEs.

Postoperative tolvaptan use in left ventricular assist device patients: The TOLVAD randomized pilot study.

PURPOSE: Tolvaptan, a selective vasopressin type-2 antagonist, has been shown to increase serum sodium (Na) and urine output in hyponatremic left ventricular assist device (LVAD) patients in retrospective studies. In this prospective randomized pilot study, we aimed to assess the efficacy of tolvaptan in this population. METHODS: We conducted a prospective, randomized, non-blinded pilot study of LVAD recipients with post-operative hyponatremia (Na < 135 mEq/L) (NCT05408104). Eligible participants were randomized to receive tolvaptan 15 mg daily in addition to usual care versus usual care alone. The primary outcome was a change in Na level and estimated glomerular filtration rate (eGFR), from the first post-operative day of hyponatremia (the day of randomization) to discharge. RESULTS: A total of 33 participants were enrolled, and 28 underwent randomization (median age 55 [IQR 50-62]), 21% women, 54% Black, 32% ischemic cardiomyopathy, median baseline Na 135 (IQR 134-138). Fifteen participants were randomized to tolvaptan (TLV) and 13 were randomized to usual care alone (No-TLV). Mean change in Na from randomization to discharge in the TLV group was 2.7 mEq/L (95%CI 0.7-4.7, p = 0.013) and 1.8 (95%CI 0.5-4.0, p = 0.11) in the No-TLV group, though baseline and final Na levels were similar between groups. The mean change in eGFR was 2.6 ml/min/1.73 m2 (95%CI 10.1-15.3, p = 0.59) in TLV versus 7.5 ml/min/1.73 m2 (95%CI 5.2-20.2, p = 0.15) in No-TLV. TLV participants had significantly more urine output than No-TLV patients during their first 24 h after randomization (3294 vs 2155 ml, p = 0.043). CONCLUSION: TLV significantly increases urine output, with nominal improvement in Na level, in hyponatremic post-operative LVAD patients without adversely impacting renal function.

Extensive pulmonary venous stenoses as a complication of radiofrequency catheter ablation for atrial fibrillation.

Although pulmonary veins stenosis (PVS) is a well documented complication of radiofrequency-catheter ablation (RFCA) of atrial fibrillation (AF), simultaneous involvement of multiple PVs is extremely rare. We present the case of a 69 years-old male patient, with prior medical history of persistent AF, who had been treated with RFCA two years ago. After RFCA, he started with shortness of breath and needed hospitalization for bilateral pneumonia. One year after the procedure, he was on home oxygen, but still referred dyspnea, cough and hemoptysis. A transthoracic echocardiogram showed moderate right ventricular (RV) systolic dysfunction and elevated RV systolic pressure. Dedicated cardiac tomography for PV assessment revealed severe narrowing and pre-stenotic engorgement of all 5 PVs, with subtotal ostial occlusion of both the left lower and right middle PVs. PV angiography confirmed the diagnosis. Only the left and right upper PV were able to be wire-crossed and stented, with substantial reductions in stenosis from 90 % to 10 %. After 3 months of follow-up, the patient improved substantially, and home O2 was withdrawn.

Biventricular Pacing Versus Right Ventricular Pacing in Patients Supported With LVAD.

OBJECTIVES: This study sought to evaluate the effects of right ventricular (RV) pacing versus biventricular (BiV) pacing on quality of life, functional status, and arrhythmias in LVAD patients. BACKGROUND: Cardiac resynchronization therapy (CRT) and left ventricular assist devices (LVADs) independently improve outcomes in heart failure patients, but the effects of combining these therapies remains unknown. We present the first prospective randomized study evaluating the effects of RV versus BiV pacing on quality of life, functional status, and arrhythmias in LVAD patients. METHODS: In this prospective randomized crossover study, LVAD patients with prior CRT devices were alternated on RV and BiV pacing for planned 7-14-day periods. Ambulatory step count, 6-minute walk test distance, Kansas City Cardiomyopathy Questionnaire scores, arrhythmia burden, CRT lead function, and echocardiographic data were collected with each pacing mode. RESULTS: Thirty patients were enrolled, with a median age of 65 years, 67% male, and mean duration of LVAD support of 309 days. Compared with BiV pacing, RV-only pacing resulted in 29% higher mean daily step count, 11% higher 6-minute walk test distance, and 7% improved KCCQ-12 score (all p < 0.03). LV end-diastolic volume was significantly lower with RV pacing (220 vs. 250 mL; p = 0.03). Fewer patients had ventricular tachyarrhythmia episodes during RV pacing (p = 0.03). RV lead impedance was lower with RV pacing (p = 0.047), but no significant differences were observed in impedance across other CRT leads. CONCLUSIONS: In the first prospective randomized study comparing variable pacing in LVAD patients, RV pacing was associated with significantly improved functional status, quality of life, fewer ventricular tachyarrhythmias, and stable lead impedance compared with BiV pacing. This study supports turning off LV lead pacing in LVAD patients with CRT.

Aortic Pulsatility Index: A Novel Hemodynamic Variable for Evaluation of Decompensated Heart Failure.

BACKGROUND: Right heart catheterization for invasive hemodynamics has shown only modest correlation with clinical outcomes. We designed a novel hemodynamic variable that incorporates ventricular output and filling pressure. We anticipated that the aortic pulsatility index (API) would correlate with clinical outcomes in patients with heart failure. METHODS AND RESULTS: We retrospectively analyzed consecutive patients undergoing right heart catheterization with milrinone drug study at our institution (February 2013 to November 2019). The API was calculated as (systolic blood pressure - diastolic blood pressure)/pulmonary capillary wedge pressure. The primary outcome was freedom from advanced therapies, defined as the need for inotropes, temporary mechanical circulatory support, a left ventricular assist device, or orthotopic heart transplantation, or death at 30 days. A total of 224 patient encounters, age 57 years (48-66 years; 34% women; 31% ischemic cardiomyopathy) were included. In univariable analysis, lower baseline API was significantly associated with progression to advanced therapies or death at 30-days (odds ratio 0.43, 95% confidence interval 0.30-0.61; P < .001) compared with those on continued medical management. Receiver operator characteristic analysis specified an optimal cutpoint of 1.45 for API. A Kaplan-Meier analysis indicated an association of API with the primary outcome (79% for API ≥ 1.45 vs 48% for API < 1.45). In multivariable analysis, higher API was strongly associated with freedom from advanced therapies or death (odds ratio 0.38, 95% confidence interval 0.22-0.65, P ≤ .001), even when adjusted for baseline characteristics and routine right heart catheterization measurements. CONCLUSIONS: The API is a novel invasive hemodynamic measurement that is associated independently with freedom from advanced therapies or death at 30-day follow-up.

Discordance between lactic acidemia and hemodynamics in patients with advanced heart failure.

BACKGROUND: Elevated lactic acid (LA) levels carry a poor prognosis in patients with shock. Data are lacking on the significance of LA levels in patients with acute decompensated heart failure (ADHF). HYPOTHESIS: This study assessed the relationship between LA levels, hemodynamics and clinical outcomes. METHODS: This was a retrospective analysis of registry data of 100 advanced heart failure patients presenting for right heart catheterization (RHC) for concern of ADHF. LA levels (normal ≤2.1 mmol/L) were obtained prior to RHC; no significant changes in therapy were made between LA collection and RHC. RESULTS: Median age was 58 (47.3, 64.8) years; 57% were receiving inotropes prior to RHC. Median pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were 28 (21, 35) mmHg and 2.0 (1.7, 2.5) L/min/m2 , respectively. Eighty patients had normal LA prior to RHC. There was no correlation between LA levels and PCWP (R = 0.09, p = .38); 63% of the normal LA group had a PCWP >24 mmHg. There was a moderate inverse correlation between LA and CI (R = - 0.40; p < .001); 58% of the normal LA group had a CI <2.2 L/min/m2 . Thirty-day survival free of death/hospice, inotrope dependence, progression to heart transplant/left-ventricular assist device implant was comparable between the normal and elevated LA groups (28% vs. 20%; p = .17). CONCLUSION: In patients presenting with ADHF, normal LA levels do not exclude the presence of depressed CI (a hemodynamic criteria for cardiogenic shock) and may not offer accurate risk stratification. Invasive hemodynamics should not be delayed based on normal LA levels alone.

Aortic pulsatility index predicts clinical outcomes in heart failure: a sub-analysis of the ESCAPE trial.

AIMS: Aortic pulsatility index (API), calculated as (systolic-diastolic blood pressure)/pulmonary capillary wedge pressure (PCWP), is a novel haemodynamic measurement representing both cardiac filling pressures and contractility. We hypothesized that API would better predict clinical outcomes than traditional haemodynamic metrics of cardiac function. METHODS AND RESULTS: The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial individual-level data were used. Routine haemodynamic measurements, including Fick cardiac index (CI), and the advanced haemodynamic metrics of API, cardiac power output (CPO), and pulmonary artery pulsatility index (PAPI) were calculated after final haemodynamic-monitored optimization. The primary outcome was a composite endpoint of death or need for orthotopic heart transplant (OHT) or left ventricular assist device (LVAD) at 6 months. A total of 433 participants were enrolled in the ESCAPE trial of which 145 had final haemodynamic data. Final API measurements predicted the primary outcome, OR 0.47 (95% CI 0.32-0.70, P < 0.001), while CI, CPO, and PAPI did not. Receiver operator characteristic analyses of final advanced haemodynamic measurements indicated API best predicted the primary outcome with a cutoff of 2.9 (sensitivity 76.2%, specificity 55.3%, correctly classified 61.4%, area-under-the-curve 0.71), compared with CPO, CI, and PAPI. Kaplan-Meier analyses indicated API ≥ 2.9 was associated with greater freedom from the primary outcome (83.5%), compared with API < 2.9 (58.4%), P = 0.001. While PAPI was also significantly associated, CI and CPO were not. CONCLUSIONS: The novel haemodynamic measurement API better predicted clinical outcomes in the ESCAPE trial when compared with traditional invasive haemodynamic metrics of cardiac function.

Heart transplantation in patients with localized prostate cancer-Are we denying a life-saving therapy due to an indolent tumor?

BACKGROUND: Prostate cancer (PC) is the most common non-cutaneous cancer in men. Approximately 90% of these cancers are localized (LPC) with a cancer-specific survival rate of 99% at 10 years. Some heart transplant centers (HTCs) regard PC as an absolute contraindication to heart transplantation (HT). This study aims to understand the current status of HT in patients with advanced heart failure (AHF) and concurrent LPC in the United States. METHODS: Adult HTCs in the United States were asked to fill out an email questionnaire addressing their current approach to HT in AHF patients with concurrent LPC. RESULTS: Fifty of the 90 HTCs that received the questionnaire responded. Only 16% of HTCs had a formal policy regarding HT in patients with LPC, while only 10% had patients with LPC on the HT waitlist at the time of the survey. Overall, 84% of the HTCs had never performed HT in a patient with LPC in the history of their transplant program. CONCLUSION: An overwhelming majority of HTCs in the United States do not consider HT an option for AHF patients with concurrent LPC and lack a formal policy regarding the same.

Neurohormonal Blockade During Left Ventricular Assist Device Support.

Neurohormonal blockade (NHB) is the mainstay of therapy for patients with systolic heart failure (HF). However, the efficacy in patients with left ventricular assist devices (LVADs) remains unknown. Of all, 114 LVAD patients (57 [48, 65] years old and 78% male) were enrolled and followed during the early period (6 months after index discharge), and 98 were followed during the late period (6-12 months following index discharge). Of them, 46% were on beta-blocker (BB), 49% on angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin II receptor blocker (ARB), and 51% on aldosterone antagonist at baseline. Prevalence of BB and ACEi/ARB use increased during the study period. During the early period, similar event rates were found irrespective of the NHB uses. During the late period, BB was associated with reduced HF readmission, and ACEi/ARB was associated with reduced HF readmission and gastrointestinal bleeding (p < 0.05 for all). In conclusion, BB and ACEi/ARB use during the late period was associated with a reduction in HF recurrence in LVAD patients. Further prospective randomized control trials are warranted to clarify the utility of NHB therapy in LVAD patients.

Cryo-EM structures of NPC1L1 reveal mechanisms of cholesterol transport and ezetimibe inhibition.

The intestinal absorption of cholesterol is mediated by a multipass membrane protein, Niemann-Pick C1-Like 1 (NPC1L1), the molecular target of a cholesterol lowering therapy ezetimibe. While ezetimibe gained Food and Drug Administration approval in 2002, its mechanism of action has remained unclear. Here, we present two cryo-electron microscopy structures of NPC1L1, one in its apo form and the other complexed with ezetimibe. The apo form represents an open state in which the N-terminal domain (NTD) interacts loosely with the rest of NPC1L1, leaving the NTD central cavity accessible for cholesterol loading. The ezetimibe-bound form signifies a closed state in which the NTD rotates ~60°, creating a continuous tunnel enabling cholesterol movement into the plasma membrane. Ezetimibe blocks cholesterol transport by occluding the tunnel instead of competing with cholesterol binding. These findings provide insight into the molecular mechanisms of NPC1L1-mediated cholesterol transport and ezetimibe inhibition, paving the way for more effective therapeutic development.

Early experience of COVID-19 in 2 heart transplant recipients: Case reports and review of treatment options.

The coronavirus disease 2019 (COVID-19) pandemic poses special challenges to immunocompromised transplant patients. Given the paucity of proven data in treating COVID-19, management of these patients is difficult, rapidly evolving, and mainly based on anecdotal experience. We report 2 cases of heart transplant (HT) recipients with COVID-19. The first is a 59-year-old female with HT in 2012 who presented on March 20, 2020 with fever, hypoxia, and ground-glass opacities on chest X-ray. She quickly progressed to acute hypoxic respiratory failure and vasoplegic shock. Despite reduction in immunosuppression and treatment with tocilizumab, intravenous immunoglobulin, hydroxychloroquine, lopinavir/ritonavir, and broad-spectrum antibiotics, she ultimately died from multiorgan failure. The second case is a 75-year-old man with HT in 2000 who presented on April 2, 2020 after curbside testing revealed positive COVID-19. Given a milder presentation compared to the first patient, antimetabolite was discontinued and only hydroxychloroquine was started. Because of a lack of clinical improvement several days later, tocilizumab, methylprednisolone, and therapeutic anticoagulation were initiated. The patient clinically improved with decreasing oxygen requirements and was discharged home. These 2 cases highlight the wide range of different presentations of COVID-19 in HT recipients and the rapidity with which the management of these patients is evolving.

Decoupling Between Diastolic Pulmonary Artery and Pulmonary Capillary Wedge Pressures Is Associated With Right Ventricular Dysfunction and Hemocompatibility-Related Adverse Events in Patients With Left Ventricular Assist Devices.

Background Decoupling between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure is an index of pulmonary vascular damage. This study assessed the impact of decoupling on right heart function and hemocompatibility-related adverse events. Methods and Results In this prospective study, patients underwent invasive hemodynamic tests following left ventricular assist device implantation. Decoupling was defined as a difference of >5 mm Hg between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure. Among 92 patients with left ventricular assist devices (median age, 61 years; 57% male), 44 patients (48%) had decoupling. Right heart function and size by echocardiographic assessment worsened during a 1-year observational period in the decoupling group as compared with the control group (P<0.05). The decoupling group had significantly lower 1-year freedom from any hemocompatibility-related adverse events (49% versus 79%; P=0.005), as well as a higher hemocompatibility score (2.14 versus 0.67; P=0.004). The scoring system depicts the severity of hemocompatibility-related adverse events using 4 escalating tiers. Increased tier I scores (1-2 gastrointestinal bleedings or medically managed pump thrombosis; P=0.027) and tier IIIB scores (disabling stroke or hemocompatibility-related adverse event-related death; P=0.041) occurred more frequently in the decoupling group. Conclusions The presence of decoupling between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure was associated with worsening of right heart function and hemocompatibility-related adverse events in patients with left ventricular assist devices.

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.

Molecular mechanism of an antagonistic antibody against glucose-dependent insulinotropic polypeptide receptor.

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone involved in regulating glucose and lipid metabolism. GIP receptor (GIPR) antagonism is believed to offer therapeutic potential for various metabolic diseases. Pharmacological intervention of GIPR, however, has limited success due to lack of effective antagonistic reagents. Previously we reported the discovery of two mouse anti-murine GIPR monoclonal antibodies (mAbs) with distinctive properties in rodent models. Here, we report the detailed structural and biochemical characterization of these two antibodies, mAb1 and mAb2. In vitro and in vivo characterizations demonstrated mAb2 is a full GIPR antagonistic antibody and mAb1 is a non-neutralizing GIPR binder. To understand the molecular basis of these two antibodies, we determined the co-crystal structures of GIPR extracellular domain in complex with mAb1 and with mAb2 at resolutions of 2.1 and 2.6 Å, respectively. While the non-neutralizing mAb1 binds to GIPR without competing with the ligand peptide, mAb2 not only partially occludes the ligand peptide binding, but also recognizes the GIPR C-terminal stalk region in a helical conformation that acts as a molecular mimic of the ligand peptide and locks GIPR in a novel auto-inhibited state. Furthermore, administration of mAb2 in diet-induced obesity mice for 7 weeks leads to both reduction in body weight gain and improvement of metabolic profiles. In contrast, mAb1 has no effect on body weight or other metabolic improvement. Together, our studies reveal the unique molecular mechanism of action underlying the superior antagonistic activity of mAb2 and signify the promising therapeutic potential of effective GIPR antagonism for the treatment of metabolic disorders.

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.

Hemodynamic Effects of Concomitant Mitral Valve Surgery and Left Ventricular Assist Device Implantation.

There are conflicting data regarding whether concomitant mitral valve surgery (MVS) at left ventricular assist device (LVAD) implantation is beneficial. This study aimed to assess the hemodynamic effects of concomitant MVS. Of all 73 enrolled patients, 44 patients had undergone concomitant MVS and 29 patients had not. Before LVAD implantation, MVS group had higher pulmonary capillary wedge pressure (p = 0.04). After LVAD implantation, MVS group had higher mean pulmonary artery pressure and cardiac output (CO). During the hemodynamic ramp study, MVS group had steeper CO slopes (0.18 [0.13 0.28] vs. 0.15 [0.08, 0.20] L/min/step; p = 0.04) at incremental LVAD speed and achieved a higher CO at the optimized set speed (5.5 [4.7, 6.9] vs. 4.9 [4.0, 5.7] L/min; p = 0.03). One-year freedom from death or heart failure readmission was statistically comparable between the two groups (61% vs. 80%, p = 0.20). Thus far, after LVAD implantation and concomitant MVS, patients had increased pulmonary hypertension, despite having higher CO and a better response of CO at incremental LVAD speed. The implication of hemodynamic features after concomitant MVS on clinical outcomes warrants further investigation.

Short-Term Efficacy and Safety of Tolvaptan in Patients with Left Ventricular Assist Devices.

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.