Predictors of developing renal dysfunction following diagnosis of transthyretin cardiac amyloidosis.

BACKGROUND: In patients with transthyretin cardiac amyloidosis (ATTR-CA), renal dysfunction is a poor prognostic indicator. Limited data are available on variables that portend worsening renal function (wRF) among ATTR-CA patients. OBJECTIVES: This study assesses which characteristics place patients at higher risk for the development of wRF (defined as a drop of ≥10% in glomerular filtration rate [GFR]) within the first year following diagnosis of ATTR-CA. METHODS: We included patients with ATTR-CA (n = 134) evaluated between 2/2016 and 12/2022 and followed for up to 1 year at our amyloid clinic. Patients were stratified into two groups: a group with maintained renal function (mRF) and a group with wRF and compared using appropriate testing. Significant variables in the univariate analysis were included in the multivariable logistic regression model to determine characteristics associated with wRF. RESULTS: Within a follow-up period of 326 ± 118 days, the median GFR% change measured -6% [-18%, +8]. About 41.8% (n = 56) had wRF, while the remainder had mRF. In addition, in patients with no prior history of chronic kidney disease (CKD), 25.5% developed de novo CKD. On multivariable logistic regression, only New York Heart Association (NYHA) class ≥III (odds ratio [OR]: 3.9, 95% confidence interval [CI]: [1.6-9.3]), history of ischemic heart disease (IHD) (OR: 0.3, 95% CI: [0.1-0.7]), and not receiving SGLT-2i (OR: 0.1, 95% CI: [0.02-0.5]) were significant predictors of wRF. CONCLUSION: Our study demonstrated that the development of de novo renal dysfunction or wRF is common following the diagnosis of ATTR-CA. Additionally, we identified worse NYHA class and no prior history of IHD as significant predictors associated with developing wRF, while receiving SGLT-2i therapy appeared to be protective in this population.

Race, Genotype, and Prognosis in Black Patients With Transthyretin Cardiac Amyloidosis.

Previous studies suggest worse outcomes in patients with variant transthyretin cardiac amyloidosis (ATTR-CA) because of valine-to-isoleucine substitution at Position 122 (V122I) (ATTRv-CA) compared with patients with wild-type (WT) disease (ATTRwt-CA). Given V122I is almost exclusively found in Black patients, it is unclear if this is attributable to the biology of genotype or racial differences. Patients with ATTR-CA diagnosed between January 2001 and August 2021 were characterized into 3 categories: (1) White with ATTRwt-CA (White-WT); (2) Black with V122I ATTRv-CA (Black-V122I), and (3) Black with ATTRwt-CA (Black-WT). Event-free survival (composite of death, left ventricular assist device, or cardiac transplant) was evaluated using univariable and multivariable analyses over a median follow-up of 1.6 (0.7 to 2.90) years. Of 694 ATTR-CA patients, 502 (72%) were White-WT, 139 Black-V122I (20%), and 53 Black-WT (8%). Notably, 28% of Black patients with ATTR-CA had WT disease and not the V122I variant. Using multivariable modeling to adjust for several prognostic features, Black-V122I had higher risk of the composite adverse outcome compared with a grouped cohort of patients with WT disease (White-WT and Black-WT) (hazard ratio [HR] 1.82, confidence interval [CI] 1.30-2.56, p < 0.001). Furthermore, the Black cohort as a whole (Black-V122I and Black-WT) demonstrated greater risk of adverse outcomes compared with White-WT (HR 1.63, CI 1.19-2.24, p = 0.002). Black-V122I had greater risk of the primary end point compared with White-WT (HR 1.80, CI 1.27-2.56, p = 0.001). Black patients with ATTR-CA have worse event-free survival than White-WT despite risk adjustment. However, it remains unclear whether this is driven by differences in race or genotype given the smaller number of Black-WT patients. Approximately one-quarter of Black patients had WT, of which a greater proportion were female compared with White-WT.

Combined Prognostic Impact of Low Muscle Mass and Hypoalbuminemia in Patients Hospitalized for Heart Failure: A Retrospective Cohort Study.

BACKGROUND: Sarcopenia and hypoalbuminemia have been identified as independent predictors of increased adverse outcomes, including mortality and readmissions, in hospitalized older adults with acute decompensated heart failure (ADHF). However, the impact of coexisting sarcopenia and hypoalbuminemia on morbidity and death in adults with ADHF has not yet been investigated. We aimed to investigate the combined effects of lower muscle mass (LMM) as a surrogate for sarcopenia and hypoalbuminemia on in-hospital and postdischarge outcomes of patients hospitalized for ADHF. METHODS AND RESULTS: A total of 385 patients admitted for ADHF between 2017 and 2020 at a single institution were retrospectively identified. Demographic and clinical data were collected, including serum albumin levels at admission and discharge. Skeletal muscle indices were derived from semi-automated segmentation software analysis on axial chest computed tomography at the twelfth vertebral level. Our analysis revealed that patients who had LMM with admission hypoalbuminemia experienced increased diagnoses of infection and delirium with longer hospital length of stay and more frequent discharge to a facility. Upon discharge, 27.9% of patients had higher muscle mass without discharge hypoalbuminemia (reference group), 9.7% had LMM without discharge hypoalbuminemia, 38.4% had higher muscle mass with discharge hypoalbuminemia, and 24.0% had LMM with discharge hypoalbuminemia; mortality rates were 37.6%, 51.4%, 48.9%, and 63.2%, respectively. 1- and 3-year mortality risks were highest in those with LMM and discharge hypoalbuminemia; this relationship remained significant over a median 23.6 (3.1-33.8) months follow-up time despite multivariable adjustments (hazard ratio, 2.03 [95% CI, 1.31-3.16]; P=0.002). CONCLUSIONS: Hospitalization with ADHF, LMM, and hypoalbuminemia portend heightened mortality risk.

Patients' and physicians' beliefs and attitudes towards integrating personalized risk estimates into patient education about left ventricular assist device therapy.

BACKGROUND: Personalized risk (PR) estimates may enhance clinical decision making and risk communication by providing individualized estimates of patient outcomes. We explored stakeholder attitudes toward the utility, acceptability, usefulness and best-practices for integrating PR estimates into patient education and decision making about Left Ventricular Assist Device (LVAD). METHODS AND RESULTS: As part of a 5-year multi-institutional AHRQ project, we conducted 40 interviews with stakeholders (physicians, nurse coordinators, patients, and caregivers), analyzed using Thematic Content Analysis. All stakeholder groups voiced positive views towards integrating PR in decision making. Patients, caregivers and coordinators emphasized that PR can help to better understand a patient's condition and risks, prepare mentally and logistically for likely outcomes, and meaningfully engage in decision making. Physicians felt it can improve their decision making by enhancing insight into outcomes, enhance tailored pre-emptive care, increase confidence in decisions, and reduce bias and subjectivity. All stakeholder groups also raised concerns about accuracy, representativeness and relevance of algorithms; predictive uncertainty; utility in relation to physician's expertise; potential negative reactions among patients; and overreliance. CONCLUSION: Stakeholders are optimistic about integrating PR into clinical decision making, but acceptability depends on prospectively demonstrating accuracy, relevance and evidence that benefits of PR outweigh potential negative impacts on decision making quality.

The spectrum of post-myocardial infarction care: From acute ischemia to heart failure.

Heart failure (HF) is the leading cause of mortality in patients with acute myocardial infarction (AMI), with incidence ranging from 14% to 36% in patients admitted due to AMI. HF post-MI develops due to complex inter-play between macrovascular obstruction, microvascular dysfunction, myocardial stunning and remodeling, inflammation, and neuro-hormonal activation. Cardiogenic shock is an extreme presentation of HF post-MI and is associated with a high mortality. Early revascularization is the only therapy shown to improve survival in patients with cardiogenic shock. Treatment of HF post-MI requires prompt recognition and timely introduction of guideline-directed therapies to improve mortality and morbidity. This article aims to provide an up-to-date review on the incidence and pathogenesis of HF post-MI, current strategies to prevent and treat onset of HF post-MI, promising therapeutic strategies, and knowledge gaps in the field.

Validation of the Minnesota Pectoralis Risk Score to predict mortality in the HeartMate 3 population.

BACKGROUND: The Minnesota Pectoralis Risk Score (MPRS) utilizes computed tomography-quantified thoracic muscle and clinical variables to predict survival after left ventricular assist device (LVAD) implantation. The model has not been prospectively tested in HeartMate 3 recipients. METHODS: A single-center HeartMate 3 cohort from July 2016 to July 2021 (n = 108) was utilized for this analysis. Cohort subjects with complete covariates for MPRS calculation (pectoralis muscle measures, Black race, creatinine, total bilirubin, body mass index, bridge to transplant status, and presence/absence of contrast) implanted after MPRS development were included. MPRS were calculated on each subject. Receiver operating characteristic curves were generated to test model discrimination at 30-day, 90-day, and 1-year mortality post-LVAD. Next, the performance of the 1-year post-LVAD outcome was compared to the HeartMate 3 survival risk score (HM3RS). RESULTS: The mean age was 58 (15 years), 80% (86/108) were male, and 26% (28/108) were destination therapy. The area under the curve (AUC) for the MPRS model to predict post-LVAD mortality was 0.73 at 30 days, 0.78 at 90 days, and 0.81 at 1 year. The AUC for the HM3RS for the 1-year outcome was 0.693. Each 1-unit point of the MPRS was associated with a significant increase in the hazard rate of death after LVAD (hazard ratio 2.1, 95% confidence interval 1.5-3.0, p < 0.0001). CONCLUSIONS: The MPRS had high performance in this prospective validation, particularly with respect to 90-day and 1-year post-LVAD mortality. Such a tool can provide additional information regarding risk stratification to aid informed decision-making.

Changes in Left Ventricular Ejection Fraction and Clinical Trajectories of Transthyretin Cardiac Amyloidosis with Systolic Dysfunction.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CM) is classically thought of as a progressive disease with preserved systolic function. The longitudinal clinical trajectories of ATTR-CM with impaired left ventricular ejection fraction (LVEF) remain unclear. METHODS: This is a single-center retrospective cohort study of consecutive patients with ATTR-CM who underwent two or more echocardiograms with baseline LVEF < 50%. Patients were stratified according to the presence of ≥5% change in LVEF. A Cox proportional hazard model examined hazard of a composite outcome of death, transplant, or LVAD insertion over the two years following diagnosis. RESULTS: In our study cohort of 179 patients, 62 patients (34.6%) experienced an increase in LVEF while 33 (18.4%) experienced a decrease in LVEF. After adjusting for covariates, patients with a decrease in EF experienced increased hazard of death (HR 2.15, 95% CI 1.05-4.40, p = 0.038) compared to those with stable or an increase in LVEF. Changes in LVEF corresponded with significant differences in NT proBNP trajectories, but initial biomarker levels or clinical staging were not predictive of LVEF trajectory. CONCLUSIONS: in ATTR-CM patients with impaired LVEF, over a third demonstrated improved LVEF over time, while those with a decrease in LVEF had worse long-term outcomes.

Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure: The ARIES-HM3 Randomized Clinical Trial.

IMPORTANCE: Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety. OBJECTIVE: To determine whether excluding aspirin as part of the antithrombotic regimen with a fully magnetically levitated LVAD is safe and decreases bleeding. DESIGN, SETTING, and PARTICIPANTS: This international, randomized, double-blind, placebo-controlled study of aspirin (100 mg/d) vs placebo with VKA therapy in patients with advanced heart failure with an LVAD was conducted across 51 centers with expertise in treating patients with advanced heart failure across 9 countries. The randomized population included 628 patients with advanced heart failure implanted with a fully magnetically levitated LVAD (314 in the placebo group and 314 in the aspirin group), of whom 296 patients in the placebo group and 293 in the aspirin group were in the primary analysis population, which informed the primary end point analysis. The study enrolled patients from July 2020 to September 2022; median follow-up was 14 months. Intervention: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg/d) or placebo in addition to an antithrombotic regimen. MAIN OUTCOMES AND MEASURES: The composite primary end point, assessed for noninferiority (-10% margin) of placebo, was survival free of a major nonsurgical (>14 days after implant) hemocompatibility-related adverse events (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months. The principal secondary end point was nonsurgical bleeding events. RESULTS: Of the 589 analyzed patients, 77% were men; one-third were Black and 61% were White. More patients were alive and free of hemocompatibility events at 12 months in the placebo group (74%) vs those taking aspirin (68%). Noninferiority of placebo was demonstrated (absolute between-group difference, 6.0% improvement in event-free survival with placebo [lower 1-sided 97.5% CI, -1.6%]; P < .001). Aspirin avoidance was associated with reduced nonsurgical bleeding events (relative risk, 0.66 [95% confidence limit, 0.51-0.85]; P = .002) with no increase in stroke or other thromboembolic events, a finding consistent among diverse subgroups of patient characteristics. CONCLUSIONS AND RELEVANCE: In patients with advanced heart failure treated with a fully magnetically levitated LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes VKA, is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069156.

Significance of Adipose Tissue Quantity and Distribution on Obesity Paradox in Heart Failure.

Obesity is a predictor of the development of systolic and diastolic heart failure (HF), but once established, patients with HF and obesity have better outcomes than their leaner counterparts, a phenomenon termed the "obesity paradox." We sought to investigate the impact of adipose tissue quantity and distribution, measured by way of computed tomography, on outcomes in patients with HF. Patients admitted for acute decompensated HF between January 2017 to December 2018 were retrospectively analyzed. Body composition measurements were made on computed tomography of the abdomen/pelvis. Visceral, subcutaneous, and intermuscular adipose tissues were measured at the mid-third lumbar vertebra, along with skeletal muscle and waist circumference. Paracardial (pericardial and epicardial) adipose tissue was measured at the mid-eight thoracic vertebra. Visceral adipose tissue index (VATI) and subcutaneous adipose tissue index (SATI), along with skeletal muscle index, were indexed for patient height. A total of 200 patients were included, 44.5% female. Body mass index and waist circumference did not significantly predict outcomes. Patients with high SATI (highest sex-stratified tertile) had significantly better survival (hazard ratio 0.58, 95% confidence interval 0.39 to 0.87, p = 0.009), whereas high VATI was nonsignificant. Patients were further divided into 4 groups based on both VATI and SATI. One- and 4-year mortality risks were lowest in those with low VATI high SATI compared with the other groups; this persisted after multivariable adjustment for covariates, including albumin and skeletal muscle index. In conclusion, the "obesity paradox" appears to be largely driven by subcutaneous adipose tissue, independent of nutrition or skeletal muscle.

Guide to Temporary Mechanical Support in Cardiogenic Shock: Choosing Wisely.

Cardiogenic shock is a multisystem pathology that carries a high mortality rate, and initial pharmacotherapies include the use of vasopressors and inotropes. These agents can increase myocardial oxygen consumption and decrease tissue perfusion that can oftentimes result in a state of refractory cardiogenic shock for which temporary mechanical circulatory support can be considered. Numerous support devices are available, each with its own hemodynamic blueprint. Defining a patient's hemodynamic profile and understanding the phenotype of cardiogenic shock is important in device selection. Careful patient selection incorporating a multidisciplinary team approach should be utilized.

Transcatheter left ventriculoplasty.

Despite significant advances in pharmacological, electrophysiological and valve therapies for heart failure with reduced ejection fraction (HFrEF), the associated morbidity, mortality and healthcare costs remain high. With a constantly growing heart failure population, the existing treatment gap between current and advanced heart failure therapies (e.g., left ventricular [LV] assist devices, heart transplantation) reflects a large unmet need, calling for novel therapeutic approaches. Left ventricular remodelling and dilatation, with or without scar formation, is the hallmark of cardiomyopathy and is associated with poor prognosis. In the era of exciting advances in structural heart interventions, the advent of minimally invasive, device-based therapies directly targeting the LV geometry and promoting physical reverse remodelling has created a new frontier in the battle against heart failure. Interventional heart failure therapy is a rapidly emerging field, encompassing structural heart and minimally invasive hybrid procedures, with two left ventriculoplasty devices currently under investigation in pivotal clinical trials in the US. This review addresses the rationale for left ventriculoplasty, presents the prior surgical and percutaneous attempts in the field, provides an overview of the novel transcatheter left ventriculoplasty devices and their respective trials, and highlights potential challenges associated with establishing such device-based therapies in our armamentarium against heart failure.

Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure: A Randomized, Placebo-Controlled, Double-Blind Study.

BACKGROUND: Evidence for modulating the sodium chloride (NaCl) intake of patients hospitalized with acute heart failure (AHF) is inconclusive. Salt restriction may not benefit; hypertonic saline may aid diuresis. OBJECTIVE: To compare the safety and efficacy of oral NaCl during intravenous (IV) diuretic therapy in renal function and weight. METHODS: Seventy hospitalized patients with AHF who were being treated with IV furosemide infusion consented to receive, randomly, 2 grams of oral NaCl or placebo 3 times a day in a double-blind manner during diuresis. Treatment efficacy (bivariate primary endpoints of change in serum creatinine levels and change in weight) was measured at 96 hours, and adverse safety events were tracked for 90 days. RESULTS: Sixty-five patients (34 NaCl, 31 placebo) were included for analysis after 5 withdrew. A median of 13 grams of NaCl was given compared to placebo. At 96 hours, there was no significant difference between treatment groups with respect to the primary endpoint (P = 0.33); however, the trial was underpowered, and there was greater than expected standard deviation in weight change. The mean change in creatinine levels and weight was 0.15 ± 0.44 mg/dL and 4.6 ± 4.2 kg in the placebo group compared with 0.04 ± 0.40 mg/dL and 4.0 ± 4.3 kg in the NaCl group (P = 0.30 and 0.57, respectively). Across efficacy and safety endpoints, we observed no significant difference between the 2 groups other than changes in serum sodium levels (-2.6 ± 2.7 in the placebo group and -0.3 ± 3.3 mEq/L in the NaCl group; P < 0.001) and in serum blood urea nitrogen levels (11 ± 15 in the placebo group; 3.1 ± 13 mEq/L in the NaCl group; P = 0.025). CONCLUSIONS: In this single-center study, liberal vs restrictive oral sodium chloride intake strategies did not impact the safety and efficacy of intravenous diuretic therapy in patients with AHF. (ClinicalTrials.gov registration NCT04334668.).

Outflow cannula alignment in continuous flow left ventricular devices is associated with stroke.

We sought to evaluate whether differences in left ventricular assist device (LVAD) canula alignment are associated with stroke. There is a paucity of clinical data on contribution of LVAD canulae alignment to strokes. We conducted a retrospective analysis of patients who underwent LVAD implantation at Houston Methodist hospital from 2011 to 2016 and included those who had undergone cardiac computed tomography (CT) with contrast. LVAD graft alignment using X-ray, echocardiography, and cardiac CT was evaluated. The primary outcome was stroke within 1 year of LVAD implantation. Of the 101 patients that underwent LVAD Implantation and cardiac CT scan during the study period, 78 met inclusion criteria. The primary outcome occurred in 12 (15.4%) patients with a median time to stroke of 77 days (interquartile range: 42-132 days). Of these, 10 patients had an ischemic and two had hemorrhagic strokes. The predominant device type was Heart Mate II (94.8%). Patients with LVAD outflow cannula to aortic angle lesser than 37.5° and those with outflow graft diameter of anastomosis less than 1.5 cm (assessed by cardiac CT) had significantly higher stroke risk (p < 0.001 and p = 0.01 respectively). In HMII patients, a lower LVAD speed at the time of CT scan was associated with stroke. Further studies are needed to identify optimal outflow graft configuration to mitigate stroke risk.

Value of psychosocial evaluation for left ventricular assist device candidates.

OBJECTIVE: Left ventricular assist devices require a psychosocial assessment to determine candidacy despite limited data correlating with outcome. Our objective is to determine whether the Stanford Integrated Psychosocial Assessment for Transplant, a tool validated for transplant and widely used by left ventricular assist device programs, predicts left ventricular assist device program hospital readmissions and death. METHODS: We performed a retrospective analysis of adults at the Cleveland Clinic with Stanford Integrated Psychosocial Assessment for Transplant scores before primary left ventricular assist device program implantation from April 1, 2013, to December 31, 2018. The primary outcome was unplanned hospital readmissions censored at death, transplantation, and transfer of care. The secondary outcome was death. RESULTS: There were 263 patients in the left ventricular assist device program with a median (Q1, Q3) Stanford Integrated Psychosocial Assessment for Transplant score of 16 (8, 28). During a median follow-up 1.2 years, 56 died, 65 underwent transplantation, and 21 had transferred care. There were 640 unplanned hospital readmissions among 250 patients with at least 1 outpatient visit at our center. In a multivariable analysis, Stanford Integrated Psychosocial Assessment for Transplant components but not total Stanford Integrated Psychosocial Assessment for Transplant score was associated with readmissions. Psychopathology (Stanford Integrated Psychosocial Assessment for Transplant C-IX) was associated with hemocompatibility (coefficient 0.21 ± standard error 0.11, P = .040) and cardiac (0.15 ± 0.065, P = .02) readmissions. Patient readiness was associated with noncardiac (Stanford Integrated Psychosocial Assessment for Transplant A-III, 0.24 ± 0.099, P = .016) and cardiac (Stanford Integrated Psychosocial Assessment for Transplant A-low total, 0.037 ± 0.014, P = .007) readmissions. Poor living environment (Stanford Integrated Psychosocial Assessment for Transplant B-VIII) was associated with device-related readmissions (0.83 ± 0.34, P = .014). Death was associated with organic psychopathology or neurocognitive impairment (Stanford Integrated Psychosocial Assessment for Transplant C-X, 0.59 ± 0.21, P = .006). CONCLUSIONS: Total Stanford Integrated Psychosocial Assessment for Transplant score was not associated with left ventricular assist device program readmission or mortality. However, we identified certain Stanford Integrated Psychosocial Assessment for Transplant components that were associated with outcome and could be used to create a left ventricular assist device program specific psychosocial tool.