How Artificial Intelligence Can Enhance the Diagnosis of Cardiac Amyloidosis: A Review of Recent Advances and Challenges.

Cardiac amyloidosis (CA) is an underdiagnosed form of infiltrative cardiomyopathy caused by abnormal amyloid fibrils deposited extracellularly in the myocardium and cardiac structures. There can be high variability in its clinical manifestations, and diagnosing CA requires expertise and often thorough evaluation; as such, the diagnosis of CA can be challenging and is often delayed. The application of artificial intelligence (AI) to different diagnostic modalities is rapidly expanding and transforming cardiovascular medicine. Advanced AI methods such as deep-learning convolutional neural networks (CNNs) may enhance the diagnostic process for CA by identifying patients at higher risk and potentially expediting the diagnosis of CA. In this review, we summarize the current state of AI applications to different diagnostic modalities used for the evaluation of CA, including their diagnostic and prognostic potential, and current challenges and limitations.

Cardiac Allograft Vasculopathy: Challenges and Advances in Invasive and Non-Invasive Diagnostic Modalities.

Cardiac allograft vasculopathy (CAV) is a distinct form of coronary artery disease that represents a major cause of death beyond the first year after heart transplantation. The pathophysiology of CAV is still not completely elucidated; it involves progressive circumferential wall thickening of both the epicardial and intramyocardial coronary arteries. Coronary angiography is still considered the gold-standard test for the diagnosis of CAV, and intravascular ultrasound (IVUS) can detect early intimal thickening with improved sensitivity. However, these tests are invasive and are unable to visualize and evaluate coronary microcirculation. Increasing evidence for non-invasive surveillance techniques assessing both epicardial and microvascular components of CAV may help improve early detection. These include computed tomography coronary angiography (CTCA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and vasodilator stress myocardial contrast echocardiography perfusion imaging. This review summarizes the current state of diagnostic modalities and their utility and prognostic value for CAV and also evaluates emerging tools that may improve the early detection of this complex disease.

Days Alive and Out of the Hospital After Heart Transplantation: A Retrospective Cohort Study.

OBJECTIVE: Evaluate days alive and out of the hospital (DAOH) as an outcome measure after orthotopic heart transplantation in patients with mechanical circulatory support (MCS) as a bridge to transplant compared to those patients without prior MCS. DESIGN: A retrospective observational study of adult patients who underwent cardiac transplantation between January 1, 2015, and January 1, 2020. The primary outcome was DAOH at 365 days (DAOH365) after an orthotopic heart transplant. A Poisson regression model was fitted to detect the association between independent variables and DAOH365. SETTING: An academic tertiary referral center. PARTICIPANTS: A total of 235 heart transplant patients were included-103 MCS as a bridge to transplant patients, and 132 direct orthotopic heart transplants without prior MCS. MEASUREMENTS AND MAIN RESULTS: The median DAOH365 for the entire cohort was 348 days (IQR 335.0-354.0). There was no difference in DAOH365 between the MCS patients and patients without MCS (347.0 days [IQR 336.0-353.0] v 348.0 days [IQR 334.0-354.0], p = 0.43). Multivariate analysis identified patients who underwent a transplant after the 2018 heart transplant allocation change, pretransplant pulmonary hypertension, and increased total ischemic time as predictors of reduced DAOH365. CONCLUSIONS: In this analysis of patients undergoing orthotopic heart transplantation, there was no significant difference in DAOH365 in patients with prior MCS as a bridge to transplant compared to those without MCS. Incorporating days alive and out of the hospital into the pre-transplant evaluation may improve understanding and conceptualization of the post-transplantation patient experience and aid in shared decision-making with clinicians.

Case report: JC polyomavirus nephropathy in simultaneous heart-kidney transplantation: the role of viral-specific in situ hybridization staining.

Introduction: JC polyomavirus (JCPyV) is a ubiquitous virus that can be latent in the brain and the kidney. It is the etiologic agent responsible for progressive multifocal leukoencephalopathy, a fatal, demyelinating disease of the central nervous system, and rarely causes polyomavirus nephropathy in immunocompromised kidney transplant recipients. Case description: We present the first case of JCPyV nephropathy in a simultaneous heart-kidney transplant patient, where viral-specific in situ hybridization staining of the kidney tissue was utilized to confirm the diagnosis. The patient was diagnosed 6 years after simultaneous heart-kidney transplantation and was treated with immunosuppression reduction and intravenous immunoglobulin. Discussion: JCPyV nephropathy should be considered in the differential diagnosis of kidney allograft injury, particularly, with suggestive light microscopy histologic features in the absence of BK polyomavirus viremia and/or viruria. In addition to obtaining JCPyV PCR in the blood, in situ hybridization staining may have a utility in confirming the diagnosis. To date, we lack effective JCPyV-specific therapies, and prompt initiation of immunosuppression reduction remains the mainstay of treatment.

Comprehensive approach to cardiac amyloidosis care: considerations in starting an amyloidosis program.

Amyloidosis is a multisystem disease which continues to present in later stages due to delayed diagnosis. Once the disease is identified, the coordination of ongoing care and treatment becomes complex and often involves multiple specialists. As knowledge of the disease grows, healthcare providers within institutions have organized to create comprehensive amyloidosis programs to better serve patients in the region. In this review, we present considerations in starting a cardiac amyloidosis program from two institutions that have recently started such programs. Identification of multidisciplinary stakeholders, development of overarching program goals, creation of institutional buy-in, and emphasis on program growth and development are tenets of a successful program. The creation and growth of an amyloidosis program has the potential to raise awareness for the disease and benefit patients and institutions alike.

ATTR Amyloidosis: Current and Emerging Management Strategies: JACC: CardioOncology State-of-the-Art Review.

Transthyretin cardiac amyloidosis (ATTR-CA) is increasingly diagnosed owing to the emergence of noninvasive imaging and improved awareness. Clinical penetrance of pathogenic alleles is not complete and therefore there is a large cohort of asymptomatic transthyretin variant carriers. Screening strategies, monitoring, and treatment of subclinical ATTR-CA requires further study. Perhaps the most important translational triumph has been the development of effective therapies that have emerged from a biological understanding of ATTR-CA pathophysiology. These include recently proven strategies of transthyretin protein stabilization and silencing of transthyretin production. Data on neurohormonal blockade in ATTR-CA are limited, with the primary focus of medical therapy on judicious fluid management. Atrial fibrillation is common and requires anticoagulation owing to the propensity for thrombus formation. Although conduction disease and ventricular arrhythmias frequently occur, little is known regarding optimal management. Finally, aortic stenosis and ATTR-CA frequently coexist, and transcatheter valve replacement is the preferred treatment approach.

Treatment of AL Amyloidosis: Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Statement 2020 Update.

Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder leading to progressive and life-threatening organ failure. The heart and the kidneys are the most commonly involved organs, but almost any organ can be involved. Because of the nonspecific presentation, diagnosis delay is common, and many patients are diagnosed with advanced organ failure. In the era of effective therapies and improved outcomes for patients with AL amyloidosis, the importance of early recognition is further enhanced as the ability to reverse organ dysfunction is limited in those with a profound organ failure. As AL amyloidosis is an uncommon disorder and given patients' frailty and high early death rate, management of this complex condition is challenging. The treatment of AL amyloidosis is based on various anti-plasma cell therapies. These therapies are borrowed and customized from the treatment of multiple myeloma, a more common disorder. However, a growing number of phase 2/3 studies dedicated to the AL amyloidosis population are being performed, making treatment decisions more evidence-based. Supportive care is an integral part of management of AL amyloidosis because of the inherent organ dysfunction, limiting the delivery of effective therapy. This extensive review brings an updated summary on the management of AL amyloidosis, sectioned into the 3 pillars for survival improvement: early disease recognition, anti-plasma cell therapy, and supportive care.

Machine learning helps predict long-term mortality and graft failure in patients undergoing heart transplant.

OBJECTIVE: We aimed to develop a risk prediction model using a machine learning to predict survival and graft failure (GF) 5 years after orthotopic heart transplant (OHT). METHODS: Using the International Society of Heart and Lung Transplant (ISHLT) registry data, we analyzed 15,236 patients who underwent OHT from January 2005 to December 2009. 342 variables were extracted and used to develop a risk prediction model utilizing a gradient-boosted machine (GBM) model to predict the risk of GF and mortality 5 years after hospital discharge. After excluding variables missing at least 50% of the observations and variables with near zero variance, 87 variables were included in the GBM model. Ten fold cross-validation repeated 5 times was used to estimate the model's external performance and optimize the hyperparameters simultaneously. Area under the receiver operator characteristic curve (AUC) for the GBM model was calculated for survival and GF 5 years post-OHT. RESULTS: The median duration of follow-up was 5 years. The mortality and GF 5 years post-OHT were 27.3% (n = 4161) and 28.1% (n = 4276), respectively. The AUC to predict 5-year mortality and GF is 0.717 (95% CI 0.696-0.737) and 0.716 (95% CI 0.696-0.736), respectively. Length of stay, recipient and donor age, recipient and donor body mass index, and ischemic time had the highest relative influence in predicting 5-year mortality and graft failure. CONCLUSION: The GBM model has a good accuracy to predict 5-year mortality and graft failure post-OHT.

Right Heart Failure: Causes and Clinical Epidemiology.

Right heart failure is a complex and diverse syndrome with unique causes and pathophysiology. The right heart is being recognized as a structurally discrete and functionally independent predictor of mortality. Renewed interest in the right heart has led to efforts to consolidate definitions of right heart failure in an effort to standardize nomenclature and unify epidemiologic studies. Improvements in imaging in particular have contributed to epidemiologic studies, as well as understanding of right heart physiology, which has subsequently led to improved diagnostics and management. This article describes the various causes of right heart disease and its epidemiology.

Progress in the Presence of Failure: Updates in Chronic Systolic Heart Failure Management.

OPINION STATEMENT: The therapeutic heart failure armamentarium has evolved from drugs to transplantation to devices through further understanding of its complex pathophysiology and pathogenesis. Current medications capitalize on our evolving understanding of the sympathetic and renin-angiotensin-aldosterone systems that subsequently promote both beneficial and maladaptive responses that ultimately yield a decrease in cardiac function. Despite these advancements, the prevalence of heart failure continues to rise and carries a significant burden on our patients and health care system. This presents a clinical dilemma on how best to care for a growing, complex, and heterogeneous cohort. Ideal treatments should decrease morbidity and mortality while providing an improvement in quality of life and functional capacity. New interventions will continue to become incorporated into everyday practice, but awareness and prevention should remain the mainstay followed by optimization of guideline-directed therapies. It is equally important to individually tailor our therapeutic approach. While strategies to treat heart failure with reduced ejection fraction continue to advance, our understanding of how best to treat specific etiologies remain in question. This review will focus on current and proposed novel interventions for the management of chronic, systolic heart failure including angiotensin receptor-neprilysin inhibitor, If channel antagonist, sodium-glucose cotransporter-2 inhibitors, and oral potassium binders.

What the Psychiatrist Needs to Know About Ventricular Assist Devices: A Comprehensive Review.

BACKGROUND: The number of patients with end-stage heart failure using mechanical circulatory support has dramatically increased over the past decade. Left ventricular assist devices, the most common type of mechanical circulatory support, can be used as a bridge to transplant, destination therapy, and as a bridge to recovery. As this patient population continues to grow, consultation-liaison psychiatrists will become increasingly involved in their care. A thorough biopsychosocial assessment is required to ensure adequate recognition and management of medical, psychiatric, social, and ethical challenges posed by this population. METHODS: We performed a literature review to identify key issues relevant to the practice of consultation-liaison psychiatrists. RESULTS: General functioning of left ventricular assist devices, device types, system components, life with a left ventricular assist device, preoperative evaluation, treatment of psychiatric comorbidities, and end-of-life decision-making are discussed. CONCLUSIONS: Consultation-liaison psychiatrists need to be familiar with the high prevalence of psychopathology in patients implanted with left ventricular assist devices. A detailed biopsychosocial formulation is required to adequately identify and, if possible, resolve a myriad of medical, psychiatric, social, and ethical challenges presented by this population. Future efforts should accurately identify and report specific psychiatric disorders and adverse events within this cohort.

Clinical Implications of Serum Albumin Levels in Acute Heart Failure: Insights From DOSE-AHF and ROSE-AHF.

BACKGROUND: Hypoalbuminemia is common in patients with chronic heart failure and, as a marker of disease severity, is associated with an adverse prognosis. Whether hypoalbuminemia contributes to (or is associated with) worse outcomes in acute heart failure (AHF) is unclear. We sought to determine the implications of low serum albumin in patients receiving decongestive therapies for AHF. METHODS AND RESULTS: Baseline serum albumin levels were measured in 456 AHF subjects randomized in the DOSE-AHF and ROSE-AHF trials. We assessed the relationship between admission albumin levels (both as a continuous variable and stratified by median albumin [≥3.5 g/dL]) and worsening renal function (WRF), worsening heart failure (WHF), and clinical decongestion by 72 hours; 7-day cardiorenal biomarkers; and post-discharge outcomes. The mean baseline albumin level was 3.5 ± 0.5 g/dL. Albumin was not associated with WRF, WHF, or clinical decongestion by 72 hours. Furthermore, there was no association between continuous albumin levels and symptom change according to visual analog scale or weight change by 72 hours. Albumin was not associated with 60-day mortality, rehospitalization, or unscheduled emergency room visits. CONCLUSIONS: Baseline serum albumin levels were not associated with short-term clinical outcomes for AHF patients undergoing decongestive therapies. These data suggest that serum albumin may not be a helpful tool to guide decongestion strategies.

Coagulopathy in Mechanical Circulatory Support: A Fine Balance.

Therapeutic intervention with mechanical circulatory support has revolutionized the medical care of individuals living with advanced heart failure. Left ventricular assist devices (LVADs) have enabled patients to live longer while providing improved quality of life and functional status. However, intervention is not without risk. Over the last decade, clinicians have identified common mechanical assist device-associated complications. This appears to be multi-factorial with relation to patient variables, inherent device technology, and nuances of concurrent medical management. This review will discuss the impact of adverse hematologic complications: bleeding, pump thrombosis, and hemolysis in continuous flow LVAD patients. These obstacles continue to pose a clinical challenge with regard to both diagnosis and optimal management. Heightened awareness and understanding of heterogeneous clinical presentations is essential for preventive management and early detection with intervention.

Biomarkers in pulmonary arterial hypertension.

Pulmonary hypertension prevalence continues to rise and remains a clinical dilemma with regards to patient recognition and management. Despite advances in our understanding of the pathophysiology and pathogenesis behind pulmonary hypertension (PH), this heterogeneous cohort continues to demonstrate significant morbidity and mortality. Biomarkers serve as a dynamic, noninvasive tool in a physician's clinical armamentarium. Their role is to impact clinical decision-making and to facilitate patient education with respect to diagnosis, prognosis, and therapeutic intervention. This review will elucidate the relationship between PH and serum biomarkers related to inflammation, myocardial dysfunction or stress, and endothelial dysfunction. Over the last two decades, the utilization and incorporation of biomarkers into the evaluation and management of pulmonary hypertension has exploded. Consequently, current guidelines and consensus documents have adopted their use. The additive roles of both established and innovative biomarkers in individuals with pulmonary arterial hypertension (PAH) will be discussed.