Machine learning and artificial intelligence are generating significant attention in the scientific community and media. Such algorithms have great potential in medicine for personalizing and ...improving patient care, including in the diagnosis and management of heart failure. Many physicians are familiar with these terms and the excitement surrounding them, but many are unfamiliar with the basics of these algorithms and how they are applied to medicine. Within heart failure research, current applications of machine learning include creating new approaches to diagnosis, classifying patients into novel phenotypic groups, and improving prediction capabilities. In this paper, we provide an overview of machine learning targeted for the practicing clinician and evaluate current applications of machine learning in the diagnosis, classification, and prediction of heart failure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aims
Worsening heart failure (HF) is associated with shorter left ventricular systolic ejection time (SET), but there are limited data describing the relationship between SET and clinical outcomes. ...Thus, the objective was to describe the association between SET and clinical outcomes in an ambulatory HF population irrespective of ejection fraction (EF).
Methods and results
We identified ambulatory patients with HF with reduced EF (HFrEF) and HF with preserved EF (HFpEF) who had an outpatient transthoracic echocardiogram performed between August 2008 and July 2010 at a tertiary referral centre. Multivariable logistic regression was used to evaluate the association between SET and 1‐year outcomes. A total of 545 HF patients (171 HFrEF, 374 HFpEF) met eligibility criteria. Compared with HFpEF, HFrEF patients were younger median age 60 years (25th–75th percentiles 50–69) vs. 64 years (25th–75th percentiles 53–74, with fewer females (30% vs. 56%) and a similar percentage of African Americans (36% vs. 35%). Median (25th–75th percentiles) EF with HFrEF was 30% (25–35%) and with HFpEF was 54% (48–58%). Median SET was shorter (280 ms vs. 315 ms, P < 0.001), median pre‐ejection period was longer (114 ms vs. 89 ms, P < 0.001), and median relaxation time was shorter (78.7 ms vs. 93.3 ms, P < 0.001) among patients with HFrEF vs. HFpEF. Death or HF hospitalization occurred in 26.9% (n = 46) HFrEF and 11.8% (n = 44) HFpEF patients. After adjustment, longer SET was associated with lower odds of the composite of death or HF hospitalization at 1 year among HFrEF but not HFpEF patients.
Conclusion
Longer SET is independently associated with improved outcomes among HFrEF patients but not HFpEF patients, supporting a potential role for normalizing SET as a therapeutic strategy with systolic dysfunction.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Anti‐beta‐1‐adrenergic receptor antibodies (anti‐β1AR Abs) have long been implicated in the pathogenesis of dilated cardiomyopathy (DCM). It is believed that these autoantibodies bind to and ...constitutively stimulate the β1AR to promote pathological cardiac remodelling and β1AR desensitization and downregulation. The prevalence of anti‐β1AR Abs in patients with DCM ranges from 26% to 60%, and the presence of these autoantibodies correlates with a poor prognosis. Several small studies have shown improvements in functional status, haemodynamics, and biomarkers of heart failure upon removal or neutralization of these antibodies from the sera of affected patients. Traditionally, removal of anti‐β1AR Abs required immunoadsorption therapy with apheresis columns directed against human immunoglobulins (Igs) and subsequent i.v. Ig infusion, thereby essentially performing a plasma exchange transfusion. However, recent advances have allowed the development of small peptides and nucleotide sequences that specifically target and neutralize anti‐β1AR Abs, providing a hopeful avenue for future drug development to treat DCM. Herein, we briefly review the clinical literature of therapy directed against anti‐β1AR Abs and highlight the opportunity for further research and development in this area.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
More than 2,400 continuous-flow left ventricular assist devices (LVADs) are implanted each year in the United States alone. Both the number of patients living with LVADs and the life expectancy of ...these patients are increasing. As a result, patients with LVADs are increasingly encountered by non-LVAD specialists who do not have training in managing advanced heart failure for general medical care, cardiovascular procedures, and other subspecialty care. An understanding of the initial evaluation and management of patients with LVADs is now an essential skill for many health care providers. In this State-of-the-Art Review, we discuss current LVAD technology, summarize our clinical experience with LVADs, and review the current data for the medical management of patients living with LVADs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Invasive hemodynamic measurement via right heart catheterization has shown divergent data in its role in the treatment of patients with heart failure (HF) and cardiogenic shock. We hypothesized that ...variation in data acquisition technique and interpretation might contribute to these observations. We sought to assess differences in hemodynamic acquisition and interpretation by operator subspecialty as well as level of experience.
Individual-level responses to how physicians both collect and interpret hemodynamic data at the time of right heart catheterization was solicited via a survey distributed to international professional societies in HF and interventional cardiology. Data were stratified both by operator subspecialty (HF specialists or interventional cardiologists IC) and operator experience (early career ≤10 years from training or late career >10 years from training) to determine variations in clinical practice. For the sensitivity analysis, we also look at differences in each subgroup. A total of 261 responses were received. There were 141 clinicians (52%) who self-identified as HF specialists, 99 (38%) identified as IC, and 20 (8%) identified as other. There were 142 early career providers (54%) and late career providers (119 46%). When recording hemodynamic values, there was considerable variation in practice patterns, regardless of subspecialty or level of experience for the majority of the intracardiac variables. There was no agreement or mild agreement among HF and IC as to when to record right atrial pressures or pulmonary capillary wedge pressures. HF cardiologists were more likely to routinely measure both Fick and thermodilution cardiac output compared with IC (51% vs 29%, P < .001), something mirrored in early career vs later career cardiologists.
Significant variation exists between the acquisition and interpretation of right heart catheterization measurements between HF and IC, as well as those early and late in their careers. With the growth of the heart team approach to management of patients in cardiogenic shock, standardization of both assessment and management practices is needed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Background
Invasive hemodynamics are fundamental in assessing patients with advanced heart failure (HF). Several novel hemodynamic parameters have been studied; however, the relative prognostic ...potential remains ill‐defined.
Hypothesis
Advanced hemodynamic parameters provide additional prognostication beyond the standard hemodynamic assessment.
Methods
Patients from the PRognostic Evaluation During Invasive CaTheterization for Heart Failure (PREDICT‐HF) registry who underwent right heart catheterization (RHC) were included in the analysis. The primary endpoint was survival to orthotopic heart transplant (OHT) or durable left ventricular assist device (LVAD), or death within 6 months of RHC.
Results
Of 846 patients included, 176 (21%) met the primary endpoint. In a multivariate model that included traditional hemodynamic variables, pulmonary capillary wedge pressure (PCWP) (OR: 1.10, 1.04−1.15, p < .001), and cardiac index (CI) (OR: 0.86, 0.81−0.92, p < .001) were shown to be predictive of adverse outcomes. In a separate multivariate model that incorporated advanced hemodynamic parameters, cardiac power output (CPO) (OR: 0.76, 0.71−0.83, p < .001), aortic pulsatility index (API) (OR: 0.94, 0.91−0.96, p < .001), and pulmonary artery pulsatility index (OR: 1.02, 1.00−1.03, p .027) were all significantly associated with the primary outcome. Positively concordant API and CPO afforded the best freedom from the endpoint (94.7%), whilst negatively concordant API and CPO had the worst freedom from the endpoint (61.5%, p < .001). Those with discordant API and CPO had similar freedom from the endpoint.
Conclusion
The advanced hemodynamic parameters API and CPO are independently associated with death or the need for OHT or LVAD within 6 months. Further prospective studies are needed to validate these parameters and elucidate their role in patients with advanced HF.
(A) Improved risk stratification of advanced heart failure using the advanced hemodynamic parameters, aortic pulsatility index (API), and cardiac power output (CPO). The simultaneous incorporation of API and CPO into risk models defines three patient populations (1 concordantly high API and CPO best prognosis, 2 discordant API and CPO intermediate prognosis, 3 concordantly low API and CPO worst prognosis) with incremental risk of the combined end‐point of death, left ventricular assist device or transplant at 6 months. (B) API and CPO measurements depicted utilizing pressure−volume loops. C. Pressure−volume loops demonstrating the relationship and utility of API and CPO in different clinical states.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background Although technological advances to pump design have improved survival, left ventricular assist device (LVAD) recipients experience variable improvements in quality of life. Methods for ...optimizing LVAD support to improve quality of life are needed. We investigated whether acoustic signatures obtained from digital stethoscopes can predict patient-centered outcomes in LVAD recipients. Methods and Results We followed precordial sounds over 6 months in 24 LVAD recipients (8 HeartWare HVAD™, 16 HeartMate 3 HM3). Subjects recorded their precordial sounds with a digital stethoscope and completed a Kansas City Cardiomyopathy Questionnaire weekly. We developed a novel algorithm to filter LVAD sounds from recordings. Unsupervised clustering of LVAD-mitigated sounds revealed distinct groups of acoustic features. Of 16 HM3 recipients, 6 (38%) had a unique acoustic feature that we have termed the pulse synchronized sound based on its temporal association with the artificial pulse of the HM3. HM3 recipients with the pulse synchronized sound had significantly better Kansas City Cardiomyopathy Questionnaire scores at baseline (median, 89.1 interquartile range, 86.2-90.4 versus 66.1 interquartile range, 31.1-73.7;
=0.03) and over the 6-month study period (marginal mean, 77.6 95% CI, 66.3-88.9 versus 59.9 95% CI, 47.9-70.0;
<0.001). Mechanistically, the pulse synchronized sound shares acoustic features with patient-derived intrinsic sounds. Finally, we developed a machine learning algorithm to automatically detect the pulse synchronized sound within precordial sounds (area under the curve, 0.95, leave-one-subject-out cross-validation). Conclusions We have identified a novel acoustic biomarker associated with better quality of life in HM3 LVAD recipients, which may provide a method for assaying optimized LVAD support.
β1-Adrenergic receptor (β1AR) stimulation confers cardioprotection via β-arrestin-de pend ent transactivation of epidermal growth factor receptors (EGFRs), however, the precise mechanism for this ...salutary process is unknown. We tested the hypothesis that the β1AR and EGFR form a complex that differentially directs intracellular signaling pathways. β1AR stimulation and EGF ligand can each induce equivalent EGFR phos pho ryl a tion, internalization, and downstream activation of ERK1/2, but only EGF ligand causes translocation of activated ERK to the nucleus, whereas β1AR-stimulated/EGFR-transactivated ERK is restricted to the cytoplasm. β1AR and EGFR are shown to interact as a receptor complex both in cell culture and endogenously in human heart, an interaction that is selective and undergoes dynamic regulation by ligand stimulation. Although catecholamine stimulation mediates the retention of β1AR-EGFR interaction throughout receptor internalization, direct EGF ligand stimulation initiates the internalization of EGFR alone. Continued interaction of β1AR with EGFR following activation is dependent upon C-terminal tail GRK phos pho ryl a tion sites of the β1AR and recruitment of β-arrestin. These data reveal a new signaling paradigm in which β-arrestin is required for the maintenance of a β1AR-EGFR interaction that can direct cytosolic targeting of ERK in response to catecholamine stimulation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Purpose of Review
To assess current management strategies for advanced heart failure in adults with congenital heart disease, including heart transplantation and mechanical circulatory support.
...Recent Findings
Current data demonstrate that adults with CHD generally experience higher short-term mortality after heart transplantation and MCS implantation, but enjoy superior long-term survival. Such patients are nonetheless less likely to receive a transplant than non-ACHD peers due to a variety of factors, including lack of applicability of current listing criteria to HF in ACHD. MCS is underutilized in ACHD, but provides similar quality of life benefits for ACHD and non-ACHD patients alike.
Summary
Heart failure in ACHD is complex and difficult to treat, and both heart transplantation and mechanical circulatory support are often challenging to implement in this patient population. However, long-term results are encouraging, and existing data supports increasing use of MCS and transplant earlier in their disease course. Multidisciplinary care is critical to success in these complex patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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