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Competing Interests: Conflicts of Interest None.

Background: Current echocardiographic risk factors for prognosis in cardiac amyloidosis (CA) do not distinguish between the two main subtypes: transthyretin cardiomyopathy (TTR) and immunoglobulin light chain cardiomyopathy (AL), each of which require distinct diagnostic and therapeutic approaches. Additionally, only traditional parameters have been studied with little data on advanced techniques. Accordingly, we sought to determine whether differences exist in 2D transthoracic echocardiography (2DE) predictors of survival between the CA subtypes using a comprehensive approach., Methods: 220 patients (72±12 years) with confirmed CA (AL=89, TTR=131) who underwent 2DE at the time of CA diagnosis were enrolled. Left ventricular (LV) dimensions, indexed mass (LVMi), global longitudinal strain (LVGLS), apical-sparing ratio (LVASR), diastology, right ventricular (RV) size and function indices including tricuspid annular systolic excursion (TAPSE), RV free-wall (RVFWS) and global (RVGLS) strain, indexed left (LA) and right atrial volumes (LAVi and RAVi), LA strain (reservoir and booster) and RV systolic pressure (RVSP) were measured. A propensity-score weighted stepwise variable selection Cox proportional hazards model derived from NYHA class and renal impairment status at diagnosis was used to determine the associations between 2DE parameters and mortality specific to CA subtype over a median follow-up of 36-months., Results: After adjusting for age, atrial fibrillation and treatment, parameters associated with survival were RVFWS (p=0.003, HR 1.15, 95% CI[1.053,1.245]) and RVSP (p=0.03, HR 1.03, 95% CI[1.004,1.063]) in AL and LVASR (p=0.007, HR 6.68, 95% CI[1.75,25.492]) and RAVi (p=0.049, HR 1.03, 95% CI[1.000,1.052]) in TTR., Conclusions: Echocardiographic prognosticators for survival are specific to cardiac amyloid subtype. These results potentially provide information critical for clinical decision-making and follow-up in these patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Karima Addetia reports financial support was provided by Pfizer Inc. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Pulmonary artery catheter haemodynamics are associated with improved survival in cardiogenic shock (CS). We investigated the utility of aortic pulsatility index (API) and cardiac power output (CPO) as surrogates for left ventricular (LV) coupling and myocardial reserve, respectively, in patients with CS undergoing dynamic assessment after a milrinone bolus., Methods and Results: Patients with SCAI Stage C CS underwent a milrinone drug study (50 mcg/kg bolus infused over 10 min) to assess inotropic response. Haemodynamic measurements were obtained at baseline and following the bolus. Aortic pulsatility index and CPO were used to risk-stratify patients with the incidence of LV assist device (LVAD), orthotopic heart transplantation (OHT), or death at 1 year as the primary composite endpoint. Two hundred and twenty-four patients in SCAI Stage C CS underwent haemodynamics prior to milrinone bolus, and 117 patients had low baseline API < 1.45. Of the 117 patients, 88 had a final API < 2.2 after milrinone load, consistent with LV decoupling, in which 73% met the composite endpoint. The remaining 29 patients had a final API ≥ 2.2 consistent with LV recoupling, and only 55% met the composite endpoint ( P = 0.046). Of the 117 patients, 40 patients had low myocardial reserve (final CPO < 0.77 W), in which 78% met the composite endpoint. Of the 77 patients who demonstrated myocardial reserve (final CPO ≥ 0.77 W), only 64% met the composite endpoint ( P = 0.039)., Conclusion: The use of API and CPO in a dynamic assessment after provocative testing led to improved risk stratification in patients with SCAI Stage C CS for clinical outcomes including LVAD, OHT, or death at 1 year., Competing Interests: Conflict of interest: J.G. is a speaker for Abbott, Medtronic, Abiomed, and CH Biomedical. C.S. is a consultant to Medtronic and Abbott; educator for Abbott. V.J. is an advisory board member for Abbott. None of the other authors have relevant disclosures., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Although impaired left ventricular (LV) global longitudinal strain (GLS) with apical sparing is a feature of cardiac amyloidosis (CA), its diagnostic accuracy has varied across studies. We aimed to determine the ability of apical sparing ratio (ASR) and most common echocardiographic parameters to differentiate patients with confirmed CA from those with clinical and/or echocardiographic suspicion of CA but with this diagnosis ruled out., Methods and Results: We identified 544 patients with confirmed CA and 200 controls (CTRLs) as defined above (CTRL patients). Measurements from transthoracic echocardiograms were performed using artificial intelligence software (Us2.AI, Singapore) and audited by an experienced echocardiographer. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance and optimal cut-offs for the differentiation of CA patients from CTRL patients. Additionally, a group of 174 healthy subjects (healthy CTRL) was included to provide insight on how patients and healthy CTRLs differed echocardiographically. LV GLS was more impaired (-13.9 ± 4.6% vs. -15.9 ± 2.7%, P < 0.0005), and ASR was higher (2.4 ± 1.2 vs. 1.7 ± 0.9, P < 0.0005) in the CA group vs. CTRL patients. Relative wall thickness and ASR were the most accurate parameters for differentiating CA from CTRL patients [area under the curve (AUC): 0.77 and 0.74, respectively]. However, even with the optimal cut-off of 1.67, ASR was only 72% sensitive and 66% specific for CA, indicating the presence of apical sparing in 32% of CTRL patients and even in 6% healthy subjects., Conclusion: Apical sparing did not prove to be a CA-specific biomarker for accurate identification of CA, when compared with clinically similar CTRLs with no CA., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Limited data exists on the prognostic impact of valvular heart disease in cardiac amyloidosis (CA). We therefore sought to define the prevalence of valvular disease in patients with CA and assess the effects of significant valve disease on survival., Methods: This multi-center retrospective cohort study included consecutive patients with confirmed transthyretin (TTR) or light chain (AL) amyloidosis. Echocardiographic data closest to the date of amyloid diagnosis was reviewed, and severity was graded according to ASE guidelines. Kaplan-Meier survival analysis was performed to compare survival between patients with moderate or greater valve disease against those with mild or less disease., Results: We included 345 patients (median age 76 years; 73 % men; 110 AL, 235TTR). The median survival for the total patient cohort with cardiac amyloidosis was 2.92 years, with 30 % of patients surviving at five years after their diagnosis. Median survival comparing AL vs ATTR was 2.58 years vs 2.82 years (p = 0.67) The most common valvular abnormalities in the total cohort were mitral (62 %) and tricuspid (66 %).regurgitation There was a statistically significant difference in median survival between patients with no or mild MR compared to those with moderate or severe MR (2.92 years vs 3.35 years, p = 0.0047) (Fig. 5). There was a statistically significant difference in median survival in patients with no or mild TR compared to those with moderate or severe TR (3.35 years vs 2.3 years, p = 0.015)., Conclusion: Our study demonstrates a significant prevalence of mitral and tricuspid regurgitation in CA, with patients with moderate to severe MR and TR having a poorer prognosis., Competing Interests: Declaration of competing interest No., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In patients with cardiac amyloidosis (CA), left ventricular ejection fraction (LVEF) is frequently preserved, despite commonly reduced global longitudinal strain (GLS). We hypothesized that nonlongitudinal contraction may initially serve as a mitigating mechanism to maintain cardiac output and studied the relationship between global circumferential (GCS) and radial (GRS) strain with LVEF and extracellular volume (ECV), a marker of amyloid burden., Methods: Patients with CA who underwent cardiac magnetic resonance (CMR; n = 140, 70.7 ± 11.5 years, 66% male) or echocardiography (n = 67, 71 ± 13 years, 66% male) and normal controls (CMR, n = 20; echocardiography, n = 45) were retrospectively identified, and GCS, GLS, and GRS were quantified using feature-tracking CMR or speckle-tracking echocardiography and compared between CA patients with preserved and reduced LVEF (CA HFpEF , CA HFrEF ) and controls. The prevalence of impaired strain (magnitudes <2.5th percentile of the controls) was compared between CA HFpEF and CA HFrEF and between ECV quartiles., Results: While echocardiography-derived GLS was impaired in both CA HFpEF (-13.4% ± 3.1%, P < .003) and CA HFrEF (-9.1% ± 3.2%, P < .003), compared with controls (-20.8% ± 2.4%), GCS was more impaired in CA HFrEF compared with both controls (-15.6% ± 5.0% vs -32.3% ± 3.3%, P < .003) and CA HFpEF (-30.4% ± 5.7%, P < .003) and did not differ between CA HFpEF and controls (P = .24). The prevalence of abnormal CMR-derived GCS (P < .0001) and GRS (P < .0001) but not GLS (P = .054) varied significantly across ECV quartiles., Conclusions: Among CA patients with preserved LVEF, preserved GCS and GRS, despite near-universally impaired GLS, may be explained by an initial predominantly subendocardial involvement, where mostly longitudinal fibers are located. If confirmed in future studies, these findings may facilitate identification of patients with early stages of CA, when treatments may be most effective., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Transthyretin amyloidosis, also called ATTR amyloidosis, is associated with accumulation of ATTR amyloid deposits in the heart and commonly manifests as progressive cardiomyopathy. Patisiran, an RNA interference therapeutic agent, inhibits the production of hepatic transthyretin., Methods: In this phase 3, double-blind, randomized trial, we assigned patients with hereditary, also known as variant, or wild-type ATTR cardiac amyloidosis, in a 1:1 ratio, to receive patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks for 12 months. A hierarchical procedure was used to test the primary and three secondary end points. The primary end point was the change from baseline in the distance covered on the 6-minute walk test at 12 months. The first secondary end point was the change from baseline to month 12 in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score (with higher scores indicating better health status). The second secondary end point was a composite of death from any cause, cardiovascular events, and change from baseline in the 6-minute walk test distance over 12 months. The third secondary end point was a composite of death from any cause, hospitalizations for any cause, and urgent heart failure visits over 12 months., Results: A total of 360 patients were randomly assigned to receive patisiran (181 patients) or placebo (179 patients). At month 12, the decline in the 6-minute walk distance was lower in the patisiran group than in the placebo group (Hodges-Lehmann estimate of median difference, 14.69 m; 95% confidence interval [CI], 0.69 to 28.69; P = 0.02); the KCCQ-OS score increased in the patisiran group and declined in the placebo group (least-squares mean difference, 3.7 points; 95% CI, 0.2 to 7.2; P = 0.04). Significant benefits were not observed for the second secondary end point. Infusion-related reactions, arthralgia, and muscle spasms occurred more often among patients in the patisiran group than among those in the placebo group., Conclusions: In this trial, administration of patisiran over a period of 12 months resulted in preserved functional capacity in patients with ATTR cardiac amyloidosis. (Funded by Alnylam Pharmaceuticals; APOLLO-B ClinicalTrials.gov number, NCT03997383.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Tricuspid regurgitation(TR) following heart transplantation could adversely affect clinical outcomes. In an effort to reduce the incidence of TR, prophylactic donor heart tricuspid valve annuloplasty has been performed during heart transplantation in our institution. We assessed early and long-term outcomes., Methods: Between August 2011 and August 2021, 349 patients who underwent prophylactic tricuspid valve annuloplasty were included. Tricuspid valve annuloplasty was performed using the DeVega annuloplasty technique. The clinical outcomes of the interests included complete atrioventricular block requiring pacemaker implantation, the occurrence of significant TR(defined as moderate or greater), and survival. Long-term survival was compared in patients with and without significant TR using the Kaplan-Meier method. The Cox proportional hazards regression with time-dependent covariate analysis was used to see if significant TR affected the long-term survival., Results: There was one patient(0.3%) who required pacemaker implantation for complete atrioventricular block. No patients developed tricuspid valve stenosis that required intervention. Significant TR developed in 31 patients(8.9%) during the follow-up period. The survival rate of patients who developed significant TR was significantly lower than that of those who did not(log rank < 0.01). Significant TR was associated with the long-term mortality(HR2.92, 95%CI 1.47-5.82, p < 0.01)., Conclusions: Prophylactic donor heart tricuspid valve annuloplasty has the potential to reduce the occurrence of significant TR and can be performed safely. The significant TR that developed in patients with prophylactic annuloplasty negatively affected survival and was an independent predictor of long-term mortality., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: It remains unknown if the left atrial appendage closure (LAAC) at the time of left ventricular assist device (LVAD) surgery can reduce ischaemic cerebrovascular accidents., Methods: Consecutive 310 patients who underwent LVAD surgery with HeartMate II or 3 between January 2012 and November 2021 were included in this study. The cohort was divided into 2 groups: patients with LAAC (group A) and without LAAC (group B). We compared the clinical outcomes including the incidence of cerebrovascular accident between 2 groups., Results: Ninety-eight patients were included in group A, and 212 patients in group B. There were no significant differences between 2 groups in age, preoperative CHADS2 score and history of atrial fibrillation. In-hospital mortality did not differ significantly between the 2 groups (group A: 7.1%, group B: 12.3%, P = 0.16). Thirty-seven patients (11.9%) experienced ischaemic cerebrovascular accident (5 patients in group A and 32 patients in group B). The cumulative incidence from ischaemic cerebrovascular accidents in group A (5.3% at 12 months and 5.3% at 36 months) was significantly lower than that in group B (8.2% at 12 months and 16.8% at 36 months; P = 0.017). In a multivariable competing risk analysis, LAAC was associated with reducing ischaemic cerebrovascular accidents (hazard ratio 0.38, 95% confidence interval 0.15-0.97, P = 0.043)., Conclusions: Concomitant LAAC in LVAD surgery can reduce ischaemic cerebrovascular accidents without increasing perioperative mortality and complications., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Competing Interests: Disclosures None.

Aims: While cardiac magnetic resonance (CMR) is often obtained early in the evaluation of suspected cardiac amyloidosis (CA), it currently cannot be utilized to differentiate immunoglobulin (AL) and transthyretin (ATTR) CA. We aimed to determine whether a novel CMR and light-chain biomarker-based algorithm could accurately diagnose ATTR-CA., Methods and Results: Patients with confirmed AL or ATTR-CA with typical late gadolinium enhancement (LGE) and Look-Locker pattern for CA on CMR were retrospectively identified at three academic medical centres. Comprehensive light-chain analysis including free light chains, serum, and urine electrophoresis/immunofixation was performed. The diagnostic accuracy of the typical CMR pattern for CA in combination with negative light chains for the diagnosis of ATTR-CA was determined both in the entire cohort and in the subset of patients with invasive tissue biopsy as the gold standard. A total of 147 patients (age 70 ± 11, 76% male, 51% black) were identified: 89 ATTR-CA and 58 AL-CA. Light-chain biomarkers were abnormal in 81 (55%) patients. Within the entire cohort, the sensitivity and specificity of a typical LGE and Look-Locker CMR pattern and negative light chains for ATTR-CA was 73 and 98%, respectively. Within the subset with biopsy-confirmed subtype, the CMR and light-chain algorithm were 69% sensitive and 98% specific., Conclusion: The combination of a typical LGE and Look-Locker pattern on CMR with negative light chains is highly specific for ATTR-CA. The successful non-invasive diagnosis of ATTR-CA using CMR has the potential to reduce diagnostic and therapeutic delays and healthcare costs for many patients., Competing Interests: Conflict of interest: The authors have no relevant conflicts of interest to disclose, (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: Conflict of interest: Dr. Slivnick receives funding from IONIS Pharmaceuticals through a young investigator grant. The other authors have no relevant conflicts of interest to disclose.

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., (© 2022 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Introduction/aims: Transthyretin amyloidosis (ATTR) proteins can infiltrate skeletal muscle and infrequently cause a myopathy. 99m Technetium-pyrophosphate ( 99m Tc-PYP) is a validated biomarker for cardiac involvement in variant and wild-type ATTR (ATTRv and ATTRwt, respectively). The aim of this study was to test the hypothesis that 99m Tc-PYP is a biomarker for muscle burden of ATTR., Methods: Radioisotope uptake in the deltoid muscles of patients with ATTR was compared to uptake in control subjects without amyloidosis in a retrospective study. 99m Tc-PYP scans were evaluated in 11 patients with ATTR (7 ATTRv, 4 ATTRwt) and 14 control subjects. Mean count (MC) values were measured in circular regions of interest (ROIs) 2.5-3.8 cm 2 in area. Tracer uptake was quantified in the heart, contralateral chest (CC), and deltoid muscles., Results: Tracer uptake was significantly higher over the deltoids and heart but not the CC, in patients with ATTR than in control subjects. MC values were 120.1 ± 43.7 (mean ± SD) in ATTR patients and 78.9 ± 20.4 in control subjects over the heart (p = 0.005), 73.3± 21.0 and 63.5 ± 14.4 over CC (p = 0.09), and 37.0 ± 11.7 and 26.0 ± 7.1 averaged over both deltoid muscles (p = 0.014)., Discussion: 99m Tc-PYP is a potential biomarker for ATTR amyloid burden in skeletal muscle., (© 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Tafamidis is the only therapy shown to improve survival in transthyretin cardiac amyloidosis (ATTR) based on randomized controlled trial data. We sought to evaluate the impact of tafamidis on survival in a real-world community-based cohort. This was a prospective observational cohort study that included consecutive patients with confirmed ATTR based on biopsy or TcPYP imaging. Baseline characteristics were compared between patients taking tafamidis vs not, and Kaplan-Meier survival analysis was performed to compare survival between these groups. We examined the reasons that ATTR patients were not on tafamidis. Of 107 ATTR patients, median age was 83.9 years, 79% were men, and 63 (59%) of them were on tafamidis. Demographics and baseline cardiovascular risk factors did not differ significantly between those on vs off tafamidis, although there was a higher proportion of NYHA Class III or IV heart failure in those off tafamidis (76% vs 57%, P < 0.01). The most common reasons patients were not on tafamidis included delays in obtaining the drug or financial barriers (59%) and NYHA Class IV heart failure (19.5%). Patients taking tafamidis had a significantly higher median survival compared to those not on tafamidis (median survival 6.70 vs 1.43 years, P < 0.0001). Our study demonstrates significantly improved survival in ATTR patients taking tafamidis. Barriers exist to tafamidis initiation including delayed access and affordability, and efforts should be made to improve patient access., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study is to investigate the early and late outcomes of axillary intra-aortic balloon pump (IABP) implantation as a bridge to heart transplantation, comparing the grafted technique with the percutaneous technique., Methods: Between July 2009 and January 2020, 163 patients underwent an axillary IABP insertion as a bridge to heart transplantation. Among them, 97 patients underwent axillary IABP implantation through a graft sutured onto the axillary artery (Group A) and 66 patients underwent percutaneously (Group B). Propensity matching identified 53 matched pairs for analysis (C-statistics 0.741). The primary outcomes of interest included IABP-related complications, success rate of a bridge to transplantation, in-hospital mortality, and late survival., Results: In the propensity-score matched cohort, there were no significant differences in the baseline characteristics between the two groups. The operation time was significantly longer in Group A than in Group B (141.5 ± 38.3 min vs 42.7 ± 19.3 min, p < 0.01). The complication rates including stroke, re-exploration for bleeding, and aortic event were not significantly different between Group A and B. However, Group A required more transfusion and re-exploration for bleeding. The success rate of a bridge to transplantation was similar between Group A (47/53, 88.7%) and Group B (47/53, 88.7%). There were no significant differences in in-hospital mortality and late survival between two groups., Conclusion: In the propensity score matching analysis, there were not any significant differences between the two groups in IABP-related complications, in-hospital mortality, and late survival. The percutaneous technique provided a shorter operation time and less requirement of transfusion and re-exploration for bleeding compared to the grafted technique. The percutaneous technique might be favorable when feasible., (© 2022. Springer Japan KK, part of Springer Nature.)

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 m 2 (95%CI 10.1-15.3, p = 0.59) in TLV versus 7.5 ml/min/1.73 m 2 (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., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: Heart failure (HF) is a prevalent chronic disease and is associated with increases in mortality and morbidity. HF is a leading cause of hospitalizations and readmissions in the United States. A potentially promising area for preventing HF readmissions is continuous remote patient monitoring (CRPM)., Objective: The primary aim of this study is to determine the feasibility and preliminary efficacy of a CRPM solution in patients with HF at NorthShore University HealthSystem., Methods: This study is a feasibility study and uses a wearable biosensor to continuously remotely monitor patients with HF for 30 days after discharge. Eligible patients admitted with an HF exacerbation at NorthShore University HealthSystem are being recruited, and the wearable biosensor is placed before discharge. The biosensor collects physiological ambulatory data, which are analyzed for signs of patient deterioration. Participants are also completing a daily survey through a dedicated study smartphone. If prespecified criteria from the physiological data and survey results are met, a notification is triggered, and a predetermined electronic health record-based pathway of telephonic management is completed. In phase 1, which has already been completed, 5 patients were enrolled and monitored for 30 days after discharge. The results of phase 1 were analyzed, and modifications to the program were made to optimize it. After analysis of the phase 1 results, 15 patients are being enrolled for phase 2, which is a calibration and testing period to enable further adjustments to be made. After phase 2, we will enroll 45 patients for phase 3. The combined results of phases 1, 2, and 3 will be analyzed to determine the feasibility of a CRPM program in patients with HF. Semistructured interviews are being conducted with key stakeholders, including patients, and these results will be analyzed using the affective adaptation of the technology acceptance model., Results: During phase 1, of the 5 patients, 2 (40%) were readmitted during the study period. The study completion rate for phase 1 was 80% (4/5), and the study attrition rate was 20% (1/5). There were 57 protocol deviations out of 150 patient days in phase 1 of the study. The results of phase 1 were analyzed, and the study protocol was adjusted to optimize it for phases 2 and 3. Phase 2 and phase 3 results will be available by the end of 2022., Conclusions: A CRPM program may offer a low-risk solution to improve care of patients with HF after hospital discharge and may help to decrease readmission of patients with HF to the hospital. This protocol may also lay the groundwork for the use of CRPM solutions in other groups of patients considered to be at high risk., International Registered Report Identifier (irrid): DERR1-10.2196/36741., (©Courtney Reamer, Wei Ning Chi, Robert Gordon, Nitasha Sarswat, Charu Gupta, Safwan Gaznabi, Emily White VanGompel, Izabella Szum, Melissa Morton-Jost, Jorma Vaughn, Karen Larimer, David Victorson, John Erwin, Lakshmi Halasyamani, Anthony Solomonides, Rema Padman, Nirav S Shah. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 25.08.2022.)

Background: Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy in which abnormally folded proteins deposit within the myocardium and the atrial walls. While left atrial dysfunction has been previously reported, the impact of CA on right atrial (RA) structure and function is unknown., Methods: We retrospectively studied 118 patients (67 immunoglobulin light chain [AL-CA], 51 transthyretin [ATTR-CA]; age, 70 ± 12 years; 57% men) who underwent transthoracic echocardiogram in sinus rhythm. Right atrial reservoir, conduit, and booster strain were quantified using speckle-tracking and compared between patients with CA and 50 healthy age-, sex-, and race-matched controls using the chi-squared or Mann-Whitney test. The relationship between RA parameters and mortality was assessed using Cox regression., Results: Right atrial volume was significantly larger in cases with CA compared with in controls: 29 (22-37) vs 21 (15-25) mL/m 2 , P < .001. Right atrial reservoir (21% [14%-35%] vs 37% [34%-43%], P < .001), conduit 11% [18%-6%] vs 14% [11%-17%], P < .001), and booster (10% [17%-5%] vs 23% [20%-27%], P < .001) strains were all significantly more impaired in the CA group compared with controls. Compared with AL-CA, ATTR-CA patients had significantly larger RA volume (34 [26-44] vs 28 [20-35] mL/m 2 , P = .005) and significantly more impaired RA reservoir (17% [10%-30%] vs 27% [17%-37%], P = .007), conduit (8% [13%-6%] vs 13% [20%-8%], P = .031), and booster (7% [14%-4%] vs 11% [18%-6%], P = .030) strain. Among CA patients, RA reservoir (hazard ratio = 0.97 per %, P = .006) and RA conduit (hazard ratio = 1.05 per %, P = .004) were significantly associated with mortality, while RA volume (P = .362) and RA booster strain (P = .180) were not., Conclusions: In CA, abnormalities in RA size and strain are highly prevalent and associated with worse prognosis, suggesting the presence of intrinsic RA atriopathy. Right atrial strain appears to be a potentially useful marker in the diagnosis, subtype differentiation, and risk stratification of CA., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: Heart transplantation involves many factors such as donor selection, recipient management, multidisciplinary assessment, coordination with other organ teams, and transportation. Because of some unpredictable factors, heart transplantation can be conducted at any time of day. The purpose of this study is to investigate if outcomes differ between heart transplants taking place inside or outside of normal working hours., Methods and Results: We reviewed patients who underwent heart transplantation at our institution from January 2010 to July 2020 (n = 329). Based on the documented start time of the recipient surgeries, the cohort was divided into two groups: working hours (Group A: 7:30 to 17:00; n = 92) and after hours (Group B: 17:00 to 7:30; n = 237). We compared these groups using propensity score matching analysis. After propensity score matching, 78 pairs of patients were successfully matched. We reviewed early and late clinical outcomes including survival. Long-term survival was compared using the Kaplan-Meier method. In the propensity-score matched patients, there were no significant differences in the baseline characteristics between two groups. In-hospital mortality was not significantly different between the two groups (Group A: 6.4% vs. Group B: 2.6%, P = 0.44). Ischaemic time and cross-clamp time did not differ between the groups. In terms of postoperative complications, there were no significant differences between two groups in stroke (6.4% vs. 3.9%, P = 0.72), primary graft dysfunction requiring extracorporeal membrane oxygenation (5.1% vs. 7.7%, P = 0.75), re-exploration for bleeding (9.0% vs. 12.8%, P = 0.44), and newly required haemodialysis (7.7% vs. 6.4%, P = 0.75). The survival rate in Group A (88.1% at 1 year, 81.3% at 3 years) was not significantly different from Group B (90.5% at 1 year, 82.3% at 3 years, log rank = 0.96)., Conclusion: There was no significant difference in clinical outcomes between heart transplants taking place inside or outside of working hours. A high quality of care can be provided for heart transplant patients even during after hours., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: Axillary Intra-aortic balloon pump (IABP) has been increasingly utilized for hemodynamic support in heart failure patients. Vascular complications associated with axillary IABP such as dissection or rupture are relatively rare but not negligible that could negatively affect clinical outcomes. We summarized our experiences., Methods: This is a retrospective study reviewing of all patients receiving an axillary IABP between June 2016 and November 2020. A total of 199 patients underwent percutaneous axillary IABP placement. 6 patients (6/199, 3.0%) were complicated with arterial/aortic dissection or rupture during the procedures or the course of treatment. We described their clinical presentations and outcomes., Results: Vascular complications included acute type A aortic dissection in 2 patients, descending aortic rupture in 1 patient, abdominal aortic rupture along with type B aortic dissection in 1 patient, and the localized left subclavian artery dissection in 2 patient. 2 type A aortic dissection cases were surgically treated: 1 with emergent left ventricle assist device and ascending aorta replacement, the other with emergent left ventricle assist device. Emergent endovascular treatment was successfully performed in 2 aortic rupture cases. The left subclavian artery dissection cases were managed medically. The postoperative/treatment course was uneventful in all patients., Conclusion: Percutaneous axillary IABP therapy can cause significant vascular complications. Early diagnosis and prompt treatment would be the key to improve the clinical outcomesv., (Copyright © 2022. Published by Elsevier Inc.)

We sought to assess the impact of the aortic root geometry on developing de novo aortic insufficiency (AI) in patients undergoing left ventricular assist device (LVAD). In total, 114 patients underwent LVAD implantation between February 2016 and January 2020 were included in this study (HeartMate3 N = 68, HeartWare N = 46). Significant aortic insufficiency was defined as mild-to-moderate or greater in echocardiography. The cohort was divided into two groups; those who developed significant AI (Group AI: n = 13) and did not (Group non-AI: n = 101). The primary outcomes of interest included late survival and predictors for significant AI. The patients in Group AI were older than Group non-AI (62.6 ± 11.9 vs 51.3 ± 14.0 years, p < 0.01). The diameter of proximal ascending aorta in Group AI was larger than Group non-AI (31.0 ± 5.0 vs 27.4 ± 4.3 mm, p < 0.01). Aortic valve remained closed in 53.8% in Group AI and 36.6% in Group non-AI (p = 0.24). The late survival was not significantly different between the groups (67.1% vs 76.0% at 3 years, log rank = 0.97). The Cox hazard model showed that larger proximal ascending aortic diameter/BSA (HR 1.55, CI 1.19-2.04, p < 0.01) and not-opening aortic valve (HR 4.73, CI 1.43-16.9, p = 0.01) were independent risk factors for significant AI. The cutoff value of proximal ascending aortic diameter/BSA was 15.5 (area under curve: 0.770, sensitivity: 0.69, specificity: 0.79). Dilated proximal ascending aorta at the time of LVAD surgery and not-opening aortic valve during follow-up were associated with the incidence of de novo significant AI., (© 2021. Springer Japan KK, part of Springer Nature.)

Abstract: Valine 122 isoleucine (V122I) is the most common mutation associated with familial transthyretin-related amyloidosis (fATTR) in the metropolitan United States. V122I-related fATTR usually presents with cardiomyopathy. When polyneuropathy is encountered, it is usually mild, distal, and axonal in nature. Although liver transplantation improves survival for fATTR neuropathy patients, neuropathy may progress post liver transplantation because of the deposition of wild-type transthyretin. We report a patient with homozygous V122I mutation who presented with asymmetrical, upper limb predominant neuropathy rather early in his disease course, which progressed for a period of 5 years after liver transplantation before stabilization with the initiation of patisiran., Competing Interests: K. Rezania has received honoraria for serving as a consultant, on the advisory board, and being a guest speaker for Akcea and Alnylam. The remaining authors report no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Dr Sarswat has been a consultant and has served on advisory boards for Alnylam, Akcea, and Pfizer; and has received grant funding from Pfizer. Dr Derman has served on an advisory board for Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Hereditary transthyretin-mediated amyloidosis, also known as ATTRv amyloidosis (v for variant), is a rare, autosomal dominant, fatal disease, in which systemic amyloid progressively impairs multiple organs, leading to disability and death. The recent approval of disease-modifying therapies offers the hope of stabilization or eventual reversal of disease progression, and yet highlights a lack of disease-management guidance. A multidisciplinary panel of expert clinicians from France and the US came to consensus on monitoring the disease and identifying progression through a clinical opinion questionnaire, a roundtable meeting, and multiple rounds of feedback., Monitoring Disease and Progression: A multidisciplinary team should monitor ATTRv amyloidosis disease course by assessing potential target organs at baseline and during follow-up for signs and symptoms of somatic and autonomic neuropathy, cardiac dysfunction and restrictive cardiomyopathy, and other manifestations. Variability in penetrance, symptoms, and course of ATTRv amyloidosis requires that all patients, regardless of variant status, undergo regular and standardized assessment in all these categories. Progression in ATTRv amyloidosis may be indicated by: worsening of several existing quantifiable symptoms or signs; the appearance of a new symptom; or the worsening of a single symptom that results in a meaningful functional impairment., Conclusions: We suggest that a multisystem approach to monitoring the signs and symptoms of ATTRv amyloidosis best captures the course of the disease. We hope this work will help form the basis of further, consensus-based guidance for the treatment of ATTRv amyloidosis., (© 2021. The Author(s).)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: We report on our experience of deploying a continuous remote patient monitoring (CRPM) study soft launch with structured cascading and escalation pathways on heart failure (HF) patients post-discharge. The lessons learned from the soft launch are used to modify and fine-tune the workflow process and study protocol., Methods: This soft launch was conducted at NorthShore University HealthSystem's Evanston Hospital from December 2020 to March 2021. Patients were provided with non-invasive wearable biosensors that continuously collect ambulatory physiological data, and a study phone that collects patient-reported outcomes. The physiological data are analyzed by machine learning algorithms, potentially identifying physiological perturbation in HF patients. Alerts from this algorithm may be cascaded with other patient status data to inform home health nurses' (HHNs') management via a structured protocol. HHNs review the monitoring platform daily. If the patient's status meets specific criteria, HHNs perform assessments and escalate patient cases to the HF team for further guidance on early intervention., Results: We enrolled five patients into the soft launch. Four participants adhered to study activities. Two out of five patients were readmitted, one due to HF, one due to infection. Observed miscommunication and protocol gaps were noted for protocol amendment. The study team adopted an organizational development method from change management theory to reconfigure the study protocol., Conclusion: We sought to automate the monitoring aspects of post-discharge care by aligning a new technology that generates streaming data from a wearable device with a complex, multi-provider workflow into a novel protocol using iterative design, implementation, and evaluation methods to monitor post-discharge HF patients. CRPM with structured escalation and telemonitoring protocol shows potential to maintain patients in their home environment and reduce HF-related readmissions. Our results suggest that further education to engage and empower frontline workers using advanced technology is essential to scale up the approach., Competing Interests: The study devices, monitoring platform, and tech support are non-financial support by physIQ. K.L. is an employee of physIQ. All other authors do not have any conflict of interest. K.L. reports employment and equity from physIQ, during the conduct of the study; other from physIQ, outside the submitted work. N.S.S. reports non-financial support from physIQ, during the conduct of the study. J.E. reports and I serve on the ACCMedAxiom Board of Trustees. This is the for-profit arm of the ACC. While I have no direct relationships with vendors, the Board approves partnerships with vendors. U.R. is funded by the Daniel F. and Ada L. Rice Foundation. The foundation is not involved in the research design, implementation, or production of the manuscript in any way. Therefore, there is no conflict of interest. W.N.C. is funded by the Daniel F. and Ada L. Rice Foundation. The foundation is not involved in the research study design, implementation, or production of the manuscript in any way. Therefore, there is no conflict of interest., (Thieme. All rights reserved.)

Background: Because transthyretin amyloid cardiomyopathy (ATTR-CM) poses unique diagnostic and therapeutic challenges, referral of patients with known or suspected disease to specialized amyloidosis centers is recommended. These centers have developed strategic practices to provide multidisciplinary comprehensive care, but their best practices have not yet been well studied as a group., Methods: A qualitative survey was conducted by telephone/email from October 2019 to February 2020 among eligible healthcare providers with experience in the management of ATTR-CM at US amyloidosis centers, patients with ATTR-CM treated at amyloidosis centers, and patient advocates from amyloidosis patient support groups., Results: Fifteen cardiologists and 9 nurse practitioners/nurses from 15 selected amyloidosis centers participated in the survey, with 16 patients and 4 patient advocates. Among participating healthcare providers, the most frequently cited center best practices were diagnostic capability, multidisciplinary care, and time spent on patient care; the greatest challenges involved coordination of patient care. Patients described the "ideal" amyloidosis program as one that provides physicians with expertise in ATTR-CM, sufficient time with patients, comprehensive patient care, and opportunities to participate in research/clinical trials. The majority of centers host patient support group meetings, and patient advocacy groups provide support for centers with physician/patient education and research., Conclusions: Amyloidosis centers offer comprehensive care based on staff expertise in ATTR-CM, a multidisciplinary approach, advanced diagnostics, and time dedicated to patient care and education. Raising awareness of amyloidosis centers' best practices among healthcare providers can reinforce the benefits of early referral and comprehensive care for patients with ATTR-CM., Competing Interests: Declaration of conflicting interests:The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JNN or his institution receives funding for research and serving on advisory boards from Alnylam, Akcea, Pfizer, and Eidos. NS has served as a consultant and participated in advisory boards for Pfizer, Alnylam, and Akcea; and has received funding for research grants from Pfizer. JF and MF have no conflicts of interest to report. YA, AC, and AH are full-time employees of Pfizer and own Pfizer stock/stock options. LK received funding from Pfizer to conduct this research and owns Pfizer stock., (© The Author(s) 2021.)

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/m 2 , 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/m 2 . 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., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

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., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)