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Although continuous-flow left ventricular assist devices (CF-LVADs) provide an augmentation in systemic perfusion, there is a scarcity of in vivo data regarding systemic pulsatility on support. Patients supported on CF-LVAD therapy (n = 71) who underwent combined left/right catheterization ramp study were included. Aortic pulsatility was defined by the pulsatile power index (PPI), which was also calculated in a cohort of high-output heart failure (HOHF, n = 66) and standard HF cohort (n = 44). PPI was drastically lower in CF-LVAD-supported patients with median PPI of 0.006 (interquartile range [IQR], 0.002-0.012) compared with PPI in the HF population at 0.09 (IQR, 0.06-0.17) or HOHF population at 0.25 (IQR, 0.13-0.37; p0.0001 among groups). With speed augmentation during ramp, PPI values fell quickly in patients with higher PPI at baseline. PPI correlated poorly with left ventricular ejection fraction (LVEF) in all groups. In CF-LVAD patients, there was a stronger correlation with LV dP/dt (r = 0.41; p = 0.001) than LVEF (r = 0.21; p = 0.08; pint0.001). CF-LVAD support is associated with a dramatic reduction in arterial pulsatility as measured by PPI relative to HOHF and HF cohorts and decreases with speed. Further work is needed to determine the applicability to the next generation of device therapy.

Cardiac sarcoidosis (CS) is a nonischemic cardiomyopathy (NICM) characterized by infiltration of noncaseating granulomas involving the heart with highly variable clinical manifestations that can include conduction abnormalities and systolic heart failure. Cardiac resynchronization therapy (CRT) has shown significant promise in NICM, though little is known about its efficacy in patients with CS.To determine if CRT improved cardiac remodeling in patients with CS.We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent CRT implantation at the Mayo Clinic enterprise from 2000 to 2021. Baseline characteristics, imaging parameters, heart failure hospitalizations and need for advanced therapies, and major adverse cardiac events (MACE) were assessed.Our cohort was comprised of 55 patients with 61.8% male and a mean age of 58.7 ± 10.9 years. Eighteen (32.7%) patients had definite CS, 21 (38.2%) had probable CS, while 16 (29.1%) had presumed CS, and 26 (47.3%) with extracardiac sarcoidosis. The majority underwent CRT-D implantation (n = 52, 94.5%) and 3 (5.5%) underwent CRT-P implantation with 67.3% of implanted devices being upgrades from prior pacemakers or implantable cardioverter defibrillators. At 6 months postimplantation there was no significant improvement in ejection fraction (34.8 ± 10.9% vs. 37.7 ± 14.2%, p = .331) or left ventricular end-diastolic diameter (58.5 ± 10.2 vs. 57.5 ± 8.1 mm, p = .236), though mild improvement in left ventricular end systolic diameter (49.1 ± 9.9 vs. 45.7± 9.9 mm, p .0001). Within the first 6 months postimplantation, 5 (9.1%) patients sustained a heart failure hospitalization. At a mean follow-up of 4.1± 3.7 years, 14 (25.5%) patients experienced a heart failure hospitalization, 11 (20.0%) underwent cardiac transplantation, 1 (1.8%) underwent left ventricular assist device implantation and 7 (12.7%) patients died.Our findings suggest variable response to CRT in patients with CS with no overall improvement in ventricular function within 6 months and a substantial proportion of patients progressing to advanced heart failure therapies.

Despite interest in left ventricular (LV) recovery, there is an absence of data on the relationship between intrinsic LV hemodynamics and both reverse remodeling on a continuous flow LV assist device (CF-LVAD) therapy. We hypothesized that the markers of intrinsic LV function would be associated with remodeling, optimization, and outcomes.Patients with continuous flow LVADs between 2015 and 2019 who underwent combined left and right heart catheterization ramp protocol at a single institution were enrolled. Patients were stratified by response to continuous flow LV assist device therapy: full responders, partial responders, or nonresponders per the Utah-Inova criteria. Hemodynamic data, including LV hemodynamics of peak LV dP/dt and tau (τ) were obtained at each phase. The 1-year heart failure hospitalization-free survival was the primary end point. Among 61 patients included in the current study 38 (62%) were classified as nonresponders, 14 as partial responders (23%), and 9 as full responders (15%). The baseline LV dP/dt and τ varied by response status (P ≤ .02) and generally correlated with reverse remodeling on linear regression. Biventricular filling pressures varied with τ and there was an interaction effect of speed on the relationship between τ and pulmonary capillary wedge pressure (P = .04). Last, τ was a prognostic marker and associated with 1-year HF hospital-free survival (odds ratio 1.04, 95% confidence interval 1.00-1.07, P = .02 per millisecond increase).Significant correlations between τ and LV dP/dt and reverse remodeling were noted, with τ serving as a prognostic marker. A higher LVAD speed was associated with a greater reliance on LVAD for unloading. Future work should focus on defining the optimal level of LVAD support in relation to LV recovery.

Undiagnosed dilated cardiomyopathy (DC) can be asymptomatic or present as sudden cardiac death, therefore pre-emptively identifying and treating patients may be beneficial. Screening for DC with echocardiography is expensive and labor intensive and standard electrocardiography (ECG) is insensitive and non-specific. The performance and applicability of artificial intelligence-enabled electrocardiography (AI-ECG) for detection of DC is unknown. Diagnostic performance of an AI algorithm in determining reduced left ventricular ejection fraction (LVEF) was evaluated in a cohort that comprised of DC and normal LVEF control patients. DC patients and controls with 12-lead ECGs and a reference LVEF measured by echocardiography performed within 30 and 180 days of the ECG respectively were enrolled. The model was tested for its sensitivity, specificity, negative predictive (NPV) and positive predictive values (PPV) based on the prevalence of DC at 1% and 5%. The cohort consisted of 421 DC cases (60% males, 57±15 years, LVEF 28±11%) and 16,025 controls (49% males, age 69 ±16 years, LVEF 62±5%). For detection of LVEF≤45%, the area under the curve (AUC) was 0.955 with a sensitivity of 98.8% and specificity 44.8%. The NPV and PPV were 100% and 1.8% at a DC prevalence of 1% and 99.9% and 8.6% at a prevalence of 5%, respectively. In conclusion AI-ECG demonstrated high sensitivity and negative predictive value for detection of DC and could be used as a simple and cost-effective screening tool with implications for screening first degree relatives of DC patients.

Objective Endomyocardial biopsy (EMB) is a useful diagnostic tool though the yield may be limited in many myocardial diseases. Data on the diagnostic yield and prognostic significance of EMB guided by abnormal electrograms (EGM-Bx) in suspected cardiac sarcoidosis (CS) are scarce. Methods Seventy-nine patients (mean age: 56 ± 12 years; 61% men) with suspected CS based on clinical and imaging features underwent right or left ventricular EGM-Bx guided by electroanatomic mapping. Tissue samples were obtained from sites with abnormal EGMs and/or abnormal cardiac imaging. The diagnostic yield of EGM-Bx was evaluated in reference to histopathologic analysis. Left ventricular assist device (LVAD) and transplantation-free survival were compared between patients with positive and negative EGM-Bx for CS. Results A total of 254 samples were obtained from abnormal EGM sites, and 126 samples from normal EGM sites guided by pre-procedure imaging findings. Abnormal histopathology was noted in 65 (26%) and 10 (8%) samples from abnormal and normal EGM sites, respectively. Histopathology confirmed CS in 16 (20%) patients, while an alternative tissue diagnosis emerged in 10 (13%) patients. Abnormal EGMs at the biopsy site had sensitivity 89% and specificity 33% for a histopathologic diagnosis of CS. LVAD and transplantation-free survival were not significantly associated with the EGM-Bx result (log-rank p = .91). Conclusion In patients with suspected CS, abnormal EGM-Bx has high sensitivity and low specificity for establishing a definite CS diagnosis. Consideration of substrate abnormalities apparent on preprocedural imaging as an adjunct for selection of biopsy sites may further improve EGM-Bx yield.

Over the last half-century, left ventricular assist device (LVAD) technology has progressed from conceptual therapy for failed cardiopulmonary bypass weaning to an accepted destination therapy for advanced heart failure. The history of LVAD engineering is defined by an initial development phase, which demonstrated the feasibility of such an approach, to the more recent three major generations of commercial devices. In this review, we explore the engineering challenges of LVADs, how they were addressed over time, and the clinical outcomes that resulted from each major technological development. The first generation of commercial LVADs were pulsatile devices, which lacked the appropriate durability due to their number of moving components and hemocompatibility. The second generation of LVADs was defined by replacement of complex, pulsatile pumps with primarily axial, continuous-flow systems with an impeller in the blood passageway. These devices experienced significant commercial success, but the presence of excessive trauma to the blood and in-situ bearing resulted in an unacceptable burden of adverse events. Third generation centrifugal-flow pumps use magnetically suspended rotors within the pump chamber. Superior outcomes with this newest generation of devices have been observed, particularly with respect to hemocompatibility-related adverse events including pump thrombosis, with fully magnetically levitated devices. The future of LVAD engineering includes wireless charging foregoing percutaneous drivelines and more advanced pump control mechanisms, including synchronization of the pump flow with the native cardiac cycle, and varying pump output based on degree of physical exertion using sensor or advanced device-level data triggers.

Background Incident liver dysfunction after left ventricular assist device implantation has been previously associated with adverse outcomes, yet data on perioperative risk markers are sparse. Methods We retrospectively reviewed consecutive patients undergoing continuous-flow left ventricular assist device implant between 2007 and 2017 at a single institution. Perioperative variables were evaluated by univariate modeling and adjusted for false discovery rate. Variables most significantly associated with incident Interagency Registry for Mechanically Assisted Circulatory Support-defined liver dysfunction (INT-LD) were evaluated using logistic regression and optimal cutpoints were defined. One-year survival was evaluated using Kaplan-Meier analysis. Results We included 359 patients (79% male; mean age 59 ± 13 years; 46% ischemic; 64% destination therapy). Lower right ventricular stroke work index at the time of right heart catheterization, higher right atrial pressure 6 hours after right heart catheterization, higher preoperative total bilirubin, longer cardiopulmonary bypass time, and greater volume of intraoperative ultrafiltration were most strongly associated with incident INT-LD (adjusted P Conclusions Right ventricular stroke work index, right heart catheterization, cardiopulmonary bypass time, and ultrafiltration were each more strongly associated with elevated risk of INT-LD after left ventricular assist device implant than total bilirubin. Therefore, optimization of right ventricular hemodynamics and minimizing cardiopulmonary bypass time and ultrafiltration could potentially reduce the risk of liver dysfunction, but these observations require prospective validation.

Data on pre-implant hemodynamic optimization before continuous flow left ventricular assist device placement (CF-LVAD) with respect to patient-centered outcomes remain limited. Consecutive patients undergoing CF-LVAD implant between 2007 and 2017 were identified. Hemodynamic variables, trends, and laboratory studies were evaluated pre-LVAD implant in a logistic regression model to identify predictors of the primary composite endpoint: the need for right ventricular assist device therapy, the requirement for hemodialysis at 90 days, and 30-day mortality. Multivariate modeling identified three variables significantly associated with the primary endpoint: right ventricular stroke work index (RVSWI), right atrial pressure (RAP), and blood urea nitrogen (BUN); all immediately pre-LVAD, p0.01. Optimal dichotomization points were 500 mmHg*ml*m-2, 12 mmHg, and 40 mg/dL. The three-component model identified an AUC of 0.77 (p0.0001) for the composite endpoint. Optimization of 2/3 parameters, 1/3, and 0/3 was associated with odds ratios of 3.5 (95% CI, 1.1-11.7), 7.2 (95% CI, 2.1-24.2), and 20.6 (95% CI, 5.3-80.6), respectively, relative to those patients who were fully optimized (3/3 parameters). The number of optimized parameters was also associated with 1-year overall survival (p = 0.02). Low RVSWI, high RAP, and high BUN were independently associated with adverse outcomes after the CF-LVAD implant, demonstrating a stepwise association with severe postimplant adverse events.

A combined right and left-sided heart catheterization (RHC/LHC) protocol was recently reported to optimize patients supported by left ventricular assist device (LVAD). Using this platform, we sought to evaluate the prognostic significance of several hemodynamic indices, including left ventricular end-diastolic pressure (LVEDP) and transaortic gradient (peak aortic pressure - peak left ventricular pressure in systole, TAG). We evaluated all patients undergoing RHC/LHC at our institution from 2015 through 2018, and comprehensive clinical data were obtained. Primary end points were (1) a composite outcome that included hospitalization or death and (2) 1-year overall survival after catheterization. Forty-two patients were included in the analysis. Optimization resulted in normalization of hemodynamic parameters; all variables were significantly improved from baseline (P ≤ .05). On univariate modeling, final LVEDP was associated with the primary end point (hazard ratio [HR], 1.2 per 1-mm Hg increase; 95% CI, 1.1-1.3; P = .002). After adjusting for LVAD speed, TAG, and cardiac index in a multivariate model, the association between LVEDP and the composite end point remained significant (HR, 1.2 per 1-mm Hg increase; 95% CI, 1.1-1.4; P = .001). In the setting of LVAD support, inadequate LV unloading was a significant marker of poor outcomes with time, suggesting that LVEDP is a central prognostic marker in this population.

Despite its clinical implications in screening and therapy, genetic testing in dilated cardiomyopathy (DCM) is underused. This study evaluated implementing a practice intervention in a heart failure clinic to automate and streamline the process of genetic testing.Eligible patients with DCM were compared for frequency of pretest genetic education and testing during pre- and postintervention periods. The intervention comprised automated prescheduling of a cardiovascular genomics e-consult that served as a placeholder for downstream, pretest education, testing, and post-test review of genetic results.Patients with DCM were more likely to undergo pretest genetic education after intervention than before intervention (33.5% vs 14.8%, P.0001). Similarly, patients with DCM were more likely to undergo genetic testing after intervention than before intervention (27.3% vs 13.0%, P = .0006). The number of patients who were diagnosed to have likely pathogenic or pathogenic genetic variants were 2 of 21 (9.5%) and 6 of 53 (11.1%) before and after intervention, respectively, and variants were present in the following genes: FLNC, TTN, DES, LMNA, PLN, and TNNT2.An intervention strategy in a heart failure clinic to increase the rates of pretest genetic education and testing in eligible patients with DCM was feasible and efficacious and may have important implications for the management of DCM.

A 77 year old man previously implanted with a HeartMate II left ventricular assist device (LVAD) as destination therapy and an implantable cardioverter defibrillator presented with a left upper lobe squamous cell lung cancer. Oncology determined that proton beam therapy was indicated for treatment, and a multidisciplinary team of radiation physicists, radiation oncologists, and LVAD providers developed a protocol to proceed safely. He was successfully treated with combined proton beam radiation therapy and reduced dose chemotherapy. This case demonstrates feasibility and considerations of proton beam therapy for malignancy relevant to patients with implantable cardiac devices including LVADs.

The expanding use of continuous-flow left ventricular assist devices (CF-LVADs) for end-stage heart failure warrants familiarity with the physiologic interaction of the device with the native circulation. Contemporary devices utilize predominantly centrifugal flow and, to a lesser extent, axial flow rotors that vary with respect to their intrinsic flow characteristics. Flow can be manipulated with adjustments to preload and afterload as in the native heart, and ascertainment of the predicted effects is provided by differential pressure-flow (H-Q) curves or loops. Valvular heart disease, especially aortic regurgitation, may significantly affect adequacy of mechanical support. In contrast, atrioventricular and ventriculoventricular timing is of less certain significance. Although beneficial effects of device therapy are typically seen due to enhanced distal perfusion, unloading of the left ventricle and atrium, and amelioration of secondary pulmonary hypertension, negative effects of CF-LVAD therapy on right ventricular filling and function, through right-sided loading and septal interaction, can make optimization challenging. Additionally, a lack of pulsatile energy provided by CF-LVAD therapy has physiologic consequences for end-organ function and may be responsible for a series of adverse effects. Rheological effects of intravascular pumps, especially shear stress exposure, result in platelet activation and hemolysis, which may result in both thrombotic and hemorrhagic consequences. Development of novel solutions for untoward device-circulatory interactions will facilitate hemodynamic support while mitigating adverse events. © 2021 American Physiological Society. Compr Physiol 12:1-37, 2021.

Little is known regarding the causes of critical illness and determinants of prognosis of patients with heart failure (HF) admitted to the modern cardiac intensive care unit (CICU). We sought to describe the epidemiology and outcomes of patients with HF admitted to the contemporary CICU.Retrospective cohort analysis of Mayo Clinic CICU patients admitted with HF from 2007 to 2018 who had left ventricular ejection fraction (LVEF) data. HF with reduced LVEF (HFrEF) was defined as a LVEF of less than 50%, and HF with preserved LVEF (HFpEF) as a LVEF of 50% or greater. In-hospital mortality was analyzed using multivariable logistic regression. Survival to 1 year was analyzed using a Kaplan-Meier analysis. We included 4012 patients, including 67.8% with HFrEF and 32.2% with HFpEF. Patients with HFrEF and HFpEF were comparable and had equivalent severity of illness. Critical care therapies were used in 59.4%, with a slight preponderance in patients with HFrEF. In-hospital mortality occurred in 12.5% of patients and was similar in HFrEF vs HFpEF. Shock and cardiac arrest were the strongest predictors of adjusted in-hospital mortality, followed by Braden skin score and serum chloride level; patients with HFrEF and HFpEF had similar adjusted mortality rates. The 1-year survival after hospital discharge was 74.5% and was slightly lower for patients with HFpEF. All-cause rehospitalization occurred in 36.6%, and 52.8% of hospital survivors died or were readmitted within 1 year.CICU patients with HF have a substantial burden of critical illness, high use of critical care therapies, and poor outcomes regardless of LVEF. This finding emphasizes the potential unmet care needs in this cohort.Patients with heart failure who require admission to the cardiac intensive care unit have high severity of illness and are at significant risk of death during and after hospitalization. These patients often require specialized critical care therapies to treat manifestations of critical illness. Patients who are admitted with cardiac arrest or shock, including those who require mechanical ventilation or vasopressors, are at particularly high risk of death. Patients' left ventricular ejection fraction is not strongly associated with the risk of death when accounting for other major predictors including frailty and laboratory abnormalities.

Procainamide is a useful agent for management of ventricular arrhythmia, however its disposition and appropriate dosing during extracorporeal membrane oxygenation (ECMO) is unknown. We report experience with continuous procainamide infusion in a critically ill adult requiring venoarterial ECMO for incessant ventricular tachycardia. Pharmacokinetic analysis of procainamide and its metabolite, N-acetylprocainamide (NAPA), was performed using serum and urine specimens. Kidney function was preserved, and sequencing of the N-acetyltransferase 2 gene revealed the patient was a phenotypic slow acetylator. Procainamide volume of distribution and half-life were calculated and found to be similar to healthy individuals. However, despite elevated serum procainamide concentrations, NAPA concentrations remained far lower in the serum and urine. The magnitude of procainamide and NAPA discordance suggested alternative contributors to the deranged pharmacokinetic profile, and we hypothesized NAPA sequestration by the ECMO circuit. Ultimately, the patient received orthotopic cardiac transplantation and was discharged home in stable condition. Procainamide should be used cautiously during ECMO, with close therapeutic drug monitoring of serum procainamide and NAPA concentrations. The achievement of therapeutic NAPA concentrations while maintaining safe serum procainamide concentrations during ECMO support may be challenging.

Obstructive left ventricular assist device (LVAD) lesions are uncommon but are being increasingly recognized, particularly with the increased use of advanced imaging modalities. While heart failure symptoms and LVAD power fluctuations have a broad differential, obstructive lesions in the LVAD circuit should be considered. We present a unique case of a patient supported on HeartWare HVAD (Medtronic Inc., Dublin, Ireland) therapy, who experienced postural dizziness with objective orthostatic hypotension and occasional ventricular tachycardia. With fluctuations in LVAD flow and power, a CT scan with three-dimensional reconstruction was obtained showing outflow graft kinking. The patient was brought to the cardiac catheterization laboratory for investigation and consideration of outflow graft intervention. However, intracardiac echocardiography revealed the presence of an inflow cannula obstruction with position changes and catheter interrogation involving the outflow cannula suggestive of a gradient across the kinked area as an unlikely cause for the presentation. This case highlights the importance of a thorough interrogation for obstructive lesions in the setting of heart failure symptoms, particularly postural symptoms, in a patient on LVAD therapy, even when not identified on routine echocardiography.

Primary malignant pericardial mesothelioma is a rare cardiac neoplasm. The authors evaluated risk factors, clinical presentation, and outcomes…, Primary malignant pericardial mesothelioma is a rare cardiac neoplasm. The authors evaluated risk factors, clinical presentation, and outcomes by reviewing all biopsy-confirmed cases at one institution. The use of multimodality imaging, detailed hemodynamic assessment for the presence of an effusive-constrictive profile, and cytology evaluation can support the diagnosis. (Level of Difficulty: Advanced.), Graphical abstract

Background: The prognostic significance of paced QRS complex morphology on surface ECG remains unclear. This study aimed to assess long-term outcomes associated with variations in the paced QRS complex. Methods: Adult patients who underwent dual-chamber pacemaker implantation with 20% or more ventricular pacing and a 12-lead ECG showing a paced complex were included. The paced QRS was analyzed in leads I and aVL. Long-term clinical and echocardiographic outcomes were compared at 5 years. Results: The study included 844 patients (43.1% female; age 75.0 ± 12.1). Patients with a longer paced QRS (pQRS) duration in lead I had a lower rate of atrial fibrillation (HR 0.80; p = 0.03) and higher rate of systolic dysfunction (HR 1.17; p

A comprehensive evaluation of left ventricular assist device (LVAD) physiology requires concomitant hemodynamic and imaging assessment. Currently, transthoracic echocardiography (TTE) is the standard diagnostic modality for device interrogation. However, TTE imaging can be limited by poor acoustic

To our knowledge, natural history has not been reported for cardiac sarcoidosis (CS) diagnosed by pathologic evaluation of the apical core at left ventricular assist device (LVAD) implantation or cardiac transplantation. We retrospectively identified 232 consecutive patients meeting CS criteria. Of these patients, 54 were diagnosed by pathologic confirmation of CS, 10 after evaluation of the apical core (LVAD implant) or explanted heart (transplant). We compared clinical characteristics at initial evaluation and outcomes for these 10 patients with those of 10 patients with known CS before LVAD implant/transplant. In the study group, five patients (50%) had confirmed extracardiac sarcoidosis before LVAD implant/transplant; five had not been diagnosed with sarcoidosis. Mean (standard deviation) left ventricular ejection fraction at initial evaluation was 23% (16%), and left ventricular end-diastolic dimension was 61 (10) mm. Four patients died during follow-up; however, no survival difference was found for the 10 patients diagnosed incidentally and the group with a previous diagnosis or institutional LVAD/transplant cohorts. Patients diagnosed with CS on pathological examination of the apical core/explanted heart may have severe dilated cardiomyopathy as the initial presentation. Outcomes for patients with CS after advanced heart failure therapies may be comparable with those of non-CS patients.

In patients with advanced heart failure (HF), temporary mechanical circulator support (TMCS) is used to improve hemodynamics, via left ventricular unloading, and end-organ function as a bridge to definitive therapy. While listed for cardiac transplantation, use of TMCS may be prolonged, preventing adequate mobility. Here, we describe the technique for placement of a percutaneous axillary intra-aortic balloon pump (IABP) using single-site arterial access to facilitate ambulation and subsequent safe removal without surgery or a closure device. Retrospective review of the experience with this approach at a single institution between September 2017 and February 2020 documented feasibility and safety. Baseline demographics, hemodynamic data, and clinical outcomes were collected. Thirty-eight patients had a total of 56 IABPs placed. There were no significant access site or cerebrovascular complications. One fifth of IABPs (21.4%) had balloon failure or migration, requiring placement of a new device, though no patients had significant complications from balloon failure. The majority (81.6%) of patients in the cohort on axillary IABP support were ambulatory and ultimately received the intended therapy (63.2% transplant, 13.2% durable left ventricular assist device, 5.3% other cardiac surgery). Percutaneous, axillary IABP is feasible and associated with an acceptable complication rate as a bridge to definitive therapy.

Sarcoidosis is a multisystem inflammatory condition with occasional cardiac involvement (CS), which may be associated with risk of venous thromboembolism (VTE). As data on VTE in CS are sparse and corticosteroid therapy has not been previously examined, we aim to determine the association between CS, corticosteroid treatment for CS, and VTE. Patients referred to our institution with concern for sarcoidosis and underwent a positron emission tomography (PET) scan were retrospectively assessed. Chi-squared and multivariate regression analyses were conducted to determine the association between a diagnosis of sarcoidosis, CS, corticosteroid use, and VTE events. Six hundred and forty nine patients were split into 3 categories: 235 with no sarcoidosis (NS), 91 with extra-cardiac sarcoidosis only (ECS), and 323 with CS (isolated CS and/or CS with extra cardiac sarcoid). Thirty nine CS, 7 ECS, and 9 NS patients developed PE while 44 CS, 3 ECS, and 18 NS patients developed DVT. On multivariate regression, neither CS nor ECS was an independent risk factor for VTE (p0.05) but corticosteroid use was independently associated with VTE (HR 3.06, p = 0.007 for PE, HR 6.21, p0.0001 for DVT). On logistic regression analysis, corticosteroid dose was found to be independently associated with both PE (p = 0.001) and DVT (p = 0.007). Optimal threshold for defining VTE risk with corticosteroid therapy was a prednisone-equivalent dose of 17.5 mg. In conclusion, contrary to previous studies, this current study found that neither sarcoidosis nor CS is an independent risk factor for VTE. Rather, corticosteroid therapy was associated with an increased risk of VTE.

Background Sarcoidosis is an infiltrative inflammatory condition affecting multiple organs, with cardiac involvement designated as cardiac sarcoidosis (CS). It has been proposed that inflammatory conditions like sarcoid increase the risk of venous thromboembolism (VTE), defined as pulmonary embolism (PE) and deep vein thrombosis (DVT) due to the hypercoagulable environment created by inflammation. Purpose Although previous studies have demonstrated an association with sarcoidosis and VTE, these studies failed to account for steroid use (crucial for sarcoid treatment) as an important confounder. Also, no major studies have been done previously assessing the risk of VTE in CS specifically. The objective of this investigation is to determine the association between CS, steroid treatment for CS, and VTE. Methods Patients referred to our institution with concern for sarcoid/CS were retrospectively assessed. Specific variables of interest including general baseline characteristics and those specific to CS were analyzed for their association with VTE development. Results Using Heart Rhythm Society guidelines, 649 patients were split into three categories: 235 with no sarcoid (NS), 91 with extra-cardiac sarcoid (ECS) only, and 323 with CS. In univariate analysis, 39 (12%) CS patients developed a PE vs 9 (4%) NS patients (OR 3.44, p=0.0003) and 44 (14%) CS patients developed DVT vs 18 (8%) NS patients (OR 1.90, p=0.02). In multivariate regression analysis however, neither CS nor ECS was an independent risk factor for VTE (p>0.05) but steroid use was a strong predictor of VTE (HR 3.12, p=0.007 for PE, HR 6.17, p17.5 mg daily on a receiver operating characteristic curve). Conclusion Contrary to previous studies, the current study found that neither sarcoidosis nor CS is an independent risk factor for VTE. Rather, steroid therapy for CS treatment leads to an increased prevalence of VTE, specifically at a dose above 17.5 mg daily. More research is required to clarify this relationship and assess the importance of steroid-sparing immunosuppressive therapy and potentially VTE prophylaxis in CS management. Steroid use and time to PE/DVT Funding Acknowledgement Type of funding source: None

Background In patients undergoing heart transplantation, significant allosensitization limits access to organs, resulting in longer wait times and high waitlist mortality. Current desensitization strategies are limited in enabling successful transplantation. Objectives The purpose of this study was to describe the cumulative experience of combined heart-liver transplantation using a novel heart-after-liver transplant (HALT) protocol resulting in profound immunologic protection. Methods Reported are the results of a clinical protocol that was instituted to transplant highly sensitized patients requiring combined heart and liver transplantation at a single institution. Patients were dual-organ listed with perceived elevated risk of rejection or markedly prolonged waitlist time due to high levels of allo-antibodies. Detailed immunological data and long-term patient and graft outcomes were obtained. Results A total of 7 patients (age 43 ± 7 years, 86% women) with high allosensitization (median calculated panel reactive antibody = 77%) underwent HALT. All had significant, unacceptable donor specific antibodies (DSA) (>4,000 mean fluorescence antibody). Prospective pre-operative flow cytometric T-cell crossmatch was positive in all, and B-cell crossmatch was positive in 5 of 7. After HALT, retrospective crossmatch (B- and T-cell) became negative in all. DSA fell dramatically; at last follow-up, all pre-formed or de novo DSA levels were insignificant at 1R rejection over a median follow-up of 48 months (interquartile range: 25 to 68 months). There was 1 death due to metastatic cancer and no significant graft dysfunction. Conclusions A heart-after-liver transplantation protocol enables successful transplantation via near-elimination of DSA and is effective in preventing adverse immunological outcomes in highly sensitized patients listed for combined heart-liver transplantation.

Background Histologic evidence is required for a definitive diagnosis of cardiac sarcoidosis (CS) by published guidelines; however, the sporadic nature of the disease may produce false negative biopsy results, causing CS to be underdiagnosed. We sought to establish a clinical category of CS absent histologic findings. Methods Patients evaluated for CS were stratified into 3 groups: probable CS and definite CS based on Heart Rhythm Society (HRS) criteria and presumed CS, ie, patients without any histologic evidence of sarcoidosis, but with unexplained high-grade atrioventricular block or ventricular arrhythmia and findings suggestive of CS on either cardiac magnetic resonance imaging or positron emission tomography. The primary end point was hospitalization-free and overall survival at 10 years. Results A total of 383 patients were included in the study: 59, definite CS; 223, probable CS; and 101, presumed CS (62, isolated CS and 39, systemic CS). Compared with patients meeting HRS criteria for CS, patients with presumed CS had lower odds of New York Heart Association class III or IV symptoms (odds ratio [OR], 0.44 [95% CI, 0.23–0.83]; P = .01) but greater odds of previous ventricular tachycardia (OR, 2.4 [95% CI, 1.4–4.0]; P = .001) or history of resuscitated sudden cardiac arrest (OR, 2.9 [95% CI, 1.0–8.6]; P = .05). Hospitalization-free and overall survival were similar among groups (P = .51 and P = .71, respectively). Conclusions Clinical categorization of patients with presumed CS identified a high-risk cohort comparable to patients with histologic evidence of disease, although caution should be exercised in reaching this diagnosis without paying due diligence to the differential diagnosis.

There is a paucity of data describing the invasive assessment of afterload and influence on cardiac output in patients supported on left ventricular assist device (LVAD) therapy. From 2015 to 2018, patients on LVAD therapy were evaluated with simultaneous left/right heart catheterization ramp study for speed optimization. Hemodynamic parameters from 31 patients without significant aortic insufficiency were analyzed. Mean central aortic pressure (MAP) was elevated at 87 ± 13 mm Hg at baseline. No direct association between MAP and cardiac index (CI) was found (r = 0.11, p = 0.20). However, variable MAP provided vastly different patterns of cardiac output response to speed increments (positive correlation, p = 0.047 for MAP80 mm Hg; negative trend, p = 0.25 for MAP100 mm Hg). Patients noted to be hypertensive (MAP90, n = 8) received nitrate therapy and experienced both improvement in biventricular filling pressures and a mean increase in CI from 2.4 to 2.9 L/min/m2 (+22%, p = 0.04) at a fixed revolutions per minute. High afterload is common in patients on LVAD therapy, is associated with poor response to ramp, and is ameliorated by nitrates. These findings serve as a foundation to evaluate the dynamic effects of high afterload and chronic vasodilator therapy in patients with durable LVADs.

The true prevalence of heart failure due to wild type transthyretin amyloidosis (ATTRwt) is likely underestimated. There is a paucity of data with regard to the management of ATTRwt-related advanced heart failure and the natural history of extracardiac ATTRwt.We conducted a retrospective cohort study of patients undergoing cardiac transplant (HTx) for ATTRwt at a single institution. Comprehensive clinical data, including baseline hemodynamic and echocardiographic characteristics, and posttransplant outcomes, were obtained.Seven patients with ATTRwt underwent HTx between 2007 and 2015. All patients were male with a mean age of 66 ± 9. Patients had a reduced ejection fraction (mean, 37 ± 14%) and elevated filling pressures pre-HTx (mean pulmonary capillary wedge pressure 22 ± 7 mm Hg) before HTx. Three-year survival was 100%; 1 patient died of pancreatic cancer 45 months post-HTx (1 death per 30.8 patient-years). Oxygen consumption (Δ +6.8 ± 4.9 mL·kg·min) and 6-minute walk distances (Δ +189 ± 60 m) improved. Symptomatic gastrointestinal involvement (n = 2) and peripheral nerve involvement (n = 4) by ATTRwt developed late.This is the first report of a series of ATTRwt patients receiving HTx in which excellent outcomes are demonstrated. Although cardiac death is averted, systemic manifestations of ATTRwt may develop posttransplantation.

Purpose Landmark work has demonstrated that the hemocompatibility-related adverse event (HRAE) burden is significantly lower with the newest centrifugal flow pump; however, no study has specifically examined this HRAE burden on the prior commercially available pumps and the impact on functional outcomes. Methods We performed a retrospective analysis of HRAE (non-surgical bleeding, thrombo-embolic event, pump thrombosis, or neurological event) burden in patients following surgical implantation of Heart-Mate II (HMII) or Heart-Ware (HW) devices through 1 year of clinical follow-up. An HRAE were categorized by the type and severity of an adverse event and then assigned a net Hemocompatibility Score (HCS) of 0 through 4 for no HRAE through life-ending or disabling HRAE. Statistical analysis included comparison of net HCS using proportional regression, as well as impact on functional outcomes [NYHA class, dyspnea score, 6-minute walk, and peak venous oxygen consumption (VO2)] Results The study cohort included a total of 331 patients, with 268 patients (81%) in the HMII group and 63 patients (19%) in HW group. The overall median age was 62.2 years; patients receiving HMII were older (median 63.5 versus 58.1years, p Conclusion Burden of HRAE does not adversely affect measures of functional capacity after device implantation. Furthermore, this did not differ with the use of prior commercially-available devices. These findings indicate that overall functional quality of life may not be significantly impacted by burden of HRAE regardless of pump technology.

Data is foundational to high-quality artificial intelligence (AI). Given that a substantial amount of clinically relevant information is embedded in unstructured data, natural language processing (NLP) plays an essential role in extracting valuable information that can benefit decision making, administration reporting, and research. Here, we share several desiderata pertaining to development and usage of NLP systems, derived from two decades of experience implementing clinical NLP at the Mayo Clinic, to inform the healthcare AI community. Using a framework, we developed as an example implementation, the desiderata emphasize the importance of a user-friendly platform, efficient collection of domain expert inputs, seamless integration with clinical data, and a highly scalable computing infrastructure.

Purpose Following implantation of continuous-flow left ventricular assist devices (CF-LVADs), mechanical offloading results in improved resting hemodynamics ; however peak exercise capacity generally does not increase substantially. The present study evaluated CF-LVAD supported patients who were invasively monitored during exercise to define parameters that underpin exercise capacity and outcomes. Methods A review of all CF-LVAD patients who underwent supine cycle ergometry exercise testing with measurement of pulmonary gas exchange during right heart catheterization (RHC) for evaluation of dyspnea at one institution between 2007 and 2018 was performed (n=22). In addition to the complete resting and exercise RHC data, additional data was extracted from the medical record including: baseline demographics, echocardiographic data, cardiopulmonary exercise testing (CPET) data, six-minute walk test (6MWT) distances, and pulmonary function test data (PFT). Results The primary outcome was death or heart failure hospitalization. Although resting filling pressures were relatively preserved, resting cardiac index (Fick) was low (2.1 ± 0.5 mL/kg/min). An impaired cardiac output reserve was present in 75% of patients. On univariate modeling, patients with exercise-induced hypoxemia (arterial oxygen saturation event-free survival (unadjusted HR 11.0, CI 2.4-57.2, p=0.003), which persisted after adjustment for RHC peak VO 2 and peak cardiac output (adjusted HR 25, CI 3.6-322, p=0.001). Conclusion Our findings suggest that exercise RHC provides additional prognostic utility over resting RHC in the CF-LVAD population.

Background Cardiac sarcoidosis (CS) is an infiltrative inflammatory condition defined by infiltration of noncaseating granulomas into the heart. Based on the location of sarcoid lesion involvement, patients can present with symptoms of congestive heart failure, arrhythmias, and even sudden cardiac death. Purpose Diagnosis of CS has been somewhat challenging, with the Heart Rhythm Society (HRS) and Japanese Ministry of Health and Welfare (JMHW) being the 2 widely accepted diagnostic guidelines. Endomyocardial biopsy is the gold standard to prove definite CS but has a low sensitivity. Imaging studies have been helpful as non-invasive methods to diagnose probable CS but these can be logistically difficult and expensive. Thus, investigating for laboratory biomarkers that can act as both diagnostic and prognostic can be crucial in how we diagnose and manage CS in the future. Methods Patients meeting HRS for CS were evaluated at a single institution (n=217). Biomarkers of interest included angiotensin-converting enzyme (ACE), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin-T, 1,25 dihydroxyvitamin D (1,25-OHVit-D), and creatinine. Biomarkers were stratified by clinical variables of interest and their association with prognosis was examined. The primary endpoint was LVAD implantation, transplantation, or death. Results Mean values on presentation were: ACE 32.9±28, ESR 12±13, CRP 7.4±19, NT-proBNP 1630±2923, Troponin-T 0.03±0.1, 1,25-OHVit-D 55.5±20, and creatinine 1.12±0.3. None of the biomarkers differed by sex, definite or probable CS, or a history of immunosuppression. ACE levels were associated with the presence of cardiac fibrosis on cardiac MRI (mean difference 14.7, p=0.032). Troponin-T (p=0.006; HR 1.06 per 0.01 ng/mL), NT-proBNP (p=0.0003; HR 1.31 per 1,000 pg/mL), and creatinine (p=0.01; HR 4.02 per mg/dL) were each associated with the primary endpoint (52/217 patients). Biomarkers associated with long term outcomes in patients with cardiac sarcoidosis Biomarker Hazard ratio P value Troponin-T 1.06 (1.02–1.11)* 0.006 NT-pro BNP 1.31 (1.15–1.48)** 0.0003 Creatinine 4.02 (1.41–9.94)*** 0.01 *Per 0.01 ng/mL change; 99th percentile upper reference limit Conclusion Troponin-T, NT-proBNP, and creatinine at presentation predict outcomes in patients with CS. Further investigation on the utility of biomarkers for assessment of disease activity and treatment response is warranted.

Given the global burden of heart failure, strategies to understand the underlying cause or to provide prognostic information are critical to reducing the morbidity and mortality associated with this highly prevalent disease. Cardiomyopathies often have a genetic cause, and the field of heart failure genetics is progressing rapidly. Through a deliberate investigation, evaluation for a familial component of cardiomyopathy can lead to increased identification of pathogenic genetic variants. Much research has also been focused on identifying markers of risk in patients with cardiomyopathy with the use of genetic testing. Advances in our understanding of genetic variants have been slightly offset by an increased recognition of the heterogeneity of disease expression. Greater breadth of genetic testing can increase the likelihood of identifying a variant of uncertain significance, which is resolved only rarely by cellular functional validation and segregation analysis. To increase the use of genetics in heart failure clinics, increased availability of genetic counsellors and other providers with experience in genetics is necessary. Ultimately, through ongoing research and increased clinical experience in cardiomyopathy genetics, an improved understanding of the disease processes will facilitate better clinical decision-making about the therapies offered, exemplifying the implementation of precision medicine. In this Review, Rosenbaum and colleagues give a broad perspective on the genetic causes of dilated cardiomyopathy to provide a context for a discussion of the pragmatic use of genetic testing in heart failure clinics for patients presenting with new-onset dilated cardiomyopathy.

Background Diastolic pulmonary gradient ( DPG ) was proposed as a better marker of pulmonary vascular remodeling compared with pulmonary vascular resistance ( PVR ) and transpulmonary gradient ( TPG ). The prognostic significance of DPG in patients requiring a left ventricular assist device ( LVAD ) remains unclear. We sought to investigate whether pre‐ LVAD DPG is a predictor of survival or right ventricular ( RV ) failure post‐ LVAD . Methods and Results We retrospectively reviewed 268 patients who underwent right heart catheterization before LVAD implantation from 2007 to 2017 and had pulmonary hypertension because of left heart disease. Patients were dichotomized using DPG ≥7 mm Hg, PVR ≥3 mm Hg, or TPG ≥12 mm Hg. The associations between these parameters and all‐cause mortality or RV failure post LVAD were assessed with Cox proportional hazards regression and Kaplan–Meier analyses. After a mean follow‐up time of 35 months, elevated DPG was associated with increased risk of RV failure (hazard ratio [ HR ]: 3.30; P =0.004, for DPG ≥7 versus DPG PVR ( HR 1.85, P =0.13 for PVR ≥3 versus PVR TPG ( HR 1.47, P =0.35, for TPG ≥12 versus TPG RV failure. Elevated DPG was not associated with mortality risk ( HR 1.16, P =0.54, for DPG ≥7 versus DPG PVR , but not TPG , was associated with higher mortality risk ( HR 1.55; P =0.026, for PVR ≥3 versus PVR Conclusions Among patients with pulmonary hypertension because of left heart disease requiring LVAD support, elevated DPG was associated with RV failure but not survival, while elevated PVR predicted mortality post LVAD implantation.

The rapidly evolving field of cardiovascular genetics has already improved the care of patients with heart failure and families. The purpose of the current review is to describe the most and provide the most pertinent updates in the field of heart failure genetics. Recent advanced in heart failure genetics have begun to not only increase the yield of testing through improving technology and use of whole exome or whole genome screening, but also enabled the improving technology and increasing use of whole exome or whole genome screening, but also enabled an enhanced understanding of the implications of results of genetic testing. For instance, new data have described differential responses to heart failure therapies based on genetic testing. Additionally, variant analysis by locus in genetic cardiomyopathies has facilitated a much-improved prognostic understanding of phenotype. Recent years have seen advancements in the understanding of the genetics of rare disorders, including pediatric-onset cardiomyopathies, previously under-investigated; restrictive cardiomyopathies; and non-compaction cardiomyopathy. The last few years have heralded not only a broader understanding of the scope of the genetics of heart failure, but have also provided notable leaps in mechanistic and prognostic understanding, which will serve as the foundation for clinical investigation and future genetic variant assessment.

Percutaneous left ventricular assist devices are approved for cardiogenic shock, but there has been increasing interest in utilizing these devices for hemodynamic support as bridge to durable mechanical circulatory support (MCS). A 63 year-old male with severe ischemic cardiomyopathy was evaluated for MCS. Given severe MR at baseline, it was felt that the Impella 5.0 device would offer the best hemodynamic optimization. Transesophageal echocardiography (TEE) showed severely enlarged left ventricle (78mm) and severe MR (effective regurgitant orifice (ERO) of 0.65cm2 and regurgitant volume (RV) of 94ml. After introduction of an Impella with TEE demonstrating correct placement, mean wedge pressure fell to 11 mmHg, lacking prominent V-waves. The severity of MR decreased to mild-moderate (ERO 0.17cm2 and RV 30 ml). He underwent LVAD implant after five days of support. This case highlights the acute hemodynamic improvements observed after implantation of an Impella 5.0 in a patient with severe ischemic cardiomyopathy and functional mitral regurgitation, illustrating the benefit of percutaneous devices as bridge to durable MCS, especially in the setting of coexistent valvular disease.