Unravelling the myriad physiologic roles of transthyretin: critical considerations for treating transthyretin amyloidosis.

Background: Transthyretin (TTR) is a highly conserved protein with crucial and broadly protective physiologic roles across organ systems and diseases. Evidence shows that TTR contributes to neuroprotection, cognition, glucose regulation, pregnancy, muscle development, and bone mineralization. In several disease states, including diabetes, Alzheimer's disease, Lewy body dementia, cerebrovascular disease, and osteoporosis, higher TTR levels may be protective.

Immune Checkpoint Inhibitor Myocarditis and Left Ventricular Systolic Dysfunction.

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but ICI myocarditis (ICI-M) remains a potentially fatal complication. The clinical implications and predictors of left ventricular ejection fraction (LVEF) <50% in ICI-M are not well understood.

Objectives: The aim of this study was to identify factors associated with LVEF <50% vs ≥50% at the time of hospitalization for ICI-M.

Longitudinal Evaluation of Immune Checkpoint Inhibitor-Induced Fatigue Syndrome by Rest, Stress, and Speckle-Tracking Strain Echocardiography.

Background: Immune checkpoint inhibitor (ICI) anti-tumor therapy is commonly associated with reports of significant fatigue. Whether ICI-induced fatigue is linked to subclinical cardiac toxicity is not well understood.

Methods: We performed a prospective observational study to monitor cardiac function following initiation of ICI in cancer patients.

Automated Assessment of Right Atrial Pressure From Ultrasound Videos Using Machine Learning.

Background: Early recognition of volume overload is essential for heart failure patients. Volume overload can often be easily treated if caught early but causes significant morbidity if unrecognized and allowed to progress. Intravascular volume status can be assessed by ultrasound-based estimation of right atrial pressure (RAP), but the availability of this diagnostic modality is limited by the need for experienced physicians to accurately interpret these scans.

Left atrial strain is reduced following trastuzumab in breast cancer patients.

Background: The effect of trastuzumab therapy on left atrial (LA) function remains largely unknown. Our aim was to assess the changes in LA strain parameters longitudinally in patients treated with trastuzumab.

Methods: We retrospectively studied 170 patients with stage I-IV HER2+ breast cancer.

Association of SARS-CoV-2 Infection and Cardiopulmonary Long COVID With Exercise Capacity and Chronotropic Incompetence Among People With HIV.

Background Postacute sequelae of COVID-19 (PASC) and HIV are both associated with reduced exercise capacity, but whether SARS-CoV-2 or PASC are associated with exercise capacity among people with HIV (PWH) is unknown. We hypothesized that PWH with PASC would have reduced exercise capacity from chronotropic incompetence. Methods and Results We conducted cross-sectional cardiopulmonary exercise testing within a COVID recovery cohort that included PWH with and without prior SARS-CoV-2 infection and people without HIV with prior SARS-CoV-2 infection (controls).

Association of SARS-CoV-2 Infection and Cardiopulmonary Long COVID with Exercise Capacity and Chronotropic Incompetence among People with HIV.

Background: Long COVID has been associated with reduced exercise capacity, but whether SARS-CoV-2 infection or Long COVID is associated with reduced exercise capacity among people with HIV (PWH) has not been reported. We hypothesized that PWH with cardiopulmonary post-acute symptoms of COVID-19 (PASC) would have reduced exercise capacity due to chronotropic incompetence.

Methods: We conducted cross-sectional cardiopulmonary exercise testing within a COVID recovery cohort that included PWH.

Reduced Exercise Capacity, Chronotropic Incompetence, and Early Systemic Inflammation in Cardiopulmonary Phenotype Long Coronavirus Disease 2019.

Background: Mechanisms underlying persistent cardiopulmonary symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (postacute sequelae of coronavirus disease 2019 [COVID-19; PASC] or "long COVID") remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity.

Methods: We conducted cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults >1 year after SARS-CoV-2 infection, compared those with and those without symptoms, and correlated findings with previously measured biomarkers.

Daratumumab Plus Bortezomib and Dexamethasone in Newly Diagnosed Systemic Light Chain Amyloidosis.

Light chain amyloidosis (AL) is a plasma cell dyscrasia characterized by organ dysfunction, morbidity, and early mortality. Daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone is now standard frontline AL therapy; however, not all patients are candidates for this intensive regimen. Given the potency of Daratumumab, we evaluated an alternative frontline regimen: daratumumab, bortezomib, and limited-duration dexamethasone (Dara-Vd).

Electrocardiogram Detection of Pulmonary Hypertension Using Deep Learning.

Background: Pulmonary hypertension (PH) is life-threatening, and often diagnosed late in its course. We aimed to evaluate if a deep learning approach using electrocardiogram (ECG) data alone can detect PH and clinically important subtypes. We asked: does an automated deep learning approach to ECG interpretation detect PH and its clinically important subtypes?

Methods And Results: Adults with right heart catheterization or an echocardiogram within 90 days of an ECG at the University of California, San Francisco (2012-2019) were retrospectively identified as PH or non-PH.

Safety and efficacy of RT234 vardenafil inhalation powder on exercise parameters in pulmonary arterial hypertension: phase II, dose-escalation study design.

Background: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by high mean pulmonary arterial pressure (≥ 20 mmHg) and remodeling of the vascular arteries. Approved therapies improve symptoms and delay clinical worsening in the long term, but they do not relieve acute exertional symptoms. RT234, a drug/device combination (Respira Therapeutics, Palo Alto, CA, USA) that delivers the phosphodiesterase 5 inhibitor vardenafil to the lungs via inhalation, has been shown to reduce pulmonary vascular resistance in patients with PAH.

Post-transplant ejection fraction and renal failure in cardiac transplant recipients: An analysis of the OPTN database.

Background: Despite improved life expectancy from a heart transplant, transplant recipients remain at high risk for renal dysfunction and failure, including end-stage kidney disease (ESKD). The onset of ESKD is a poor prognostic marker and is associated with increased mortality in this setting, as in others. There is a need to identify risk factors for ESKD among heart transplant recipients in contemporary settings.

Use of Cardiopulmonary Exercise Testing to Evaluate Long COVID-19 Symptoms in Adults: A Systematic Review and Meta-analysis.

Importance: Reduced exercise capacity is commonly reported among individuals with COVID-19 symptoms more than 3 months after SARS-CoV-2 infection (long COVID-19 [LC]). Cardiopulmonary exercise testing (CPET) is the criterion standard to measure exercise capacity and identify patterns of exertional intolerance.

Objectives: To estimate the difference in exercise capacity among individuals with and without LC symptoms and characterize physiological patterns of limitations to elucidate possible mechanisms of LC.

Cardiopulmonary exercise testing to evaluate post-acute sequelae of COVID-19 ("Long COVID"): a systematic review and meta-analysis.

Importance: Reduced exercise capacity is commonly reported among individuals with Long COVID (LC). Cardiopulmonary exercise testing (CPET) is the gold-standard to measure exercise capacity to identify causes of exertional intolerance.

Objectives: To estimate the effect of SARS-CoV-2 infection on exercise capacity including those with and without LC symptoms and to characterize physiologic patterns of limitations to elucidate possible mechanisms of LC.

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID.

Background: Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 "PASC" or "Long COVID") remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity using advanced cardiac testing.

Methods: We performed cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults > 1 year after confirmed SARS-CoV-2 infection in Long-Term Impact of Infection with Novel Coronavirus cohort (LIINC; substudy of NCT04362150 ).

Mechanisms and clinical manifestations of cardiovascular toxicities associated with immune checkpoint inhibitors.

Immunotherapies have greatly expanded the armamentarium of cancer-directed therapies in the past decade, allowing the immune system to recognize and fight cancer. Immune checkpoint inhibitors (ICIs), in particular, have revolutionized cancer treatment and have demonstrated survival benefit in numerous types of cancer. These monoclonal antibodies increase anti-cancer immunity by blocking down-regulators of adaptive immunity, including cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and its ligand (PD-L1), resulting in anti-tumor activity.

Pulmonary Hypertension Due to Left Heart Disease: an Update.

Purpose Of Review: Pulmonary hypertension (PH) frequently complicates heart failure and portends a worse prognosis. This review will summarize and discuss recent updates in the classification and management of patients with PH due to left heart disease.

Recent Findings: Careful hemodynamic assessment is critical to the classification of patients with PH and heart failure.

Noninvasive estimation of pulmonary vascular resistance improves portopulmonary hypertension screening in liver transplant candidates.

Despite limitations in sensitivity and specificity, estimation of the pulmonary artery systolic pressure (ePASP) on echocardiography is used for portopulmonary hypertension (PoPH) screening in liver transplant (LT) candidates. We proposed that alternative echocardiographic models, such as estimated pulmonary vascular resistance (ePVR), may provide improved testing characteristics in PoPH screening. In a retrospective analysis of 100 LT candidates, we found that the formula ePVR = ePASP/VTI  + 3 if MSN (VTI  = right ventricular outflow tract time velocity integral; MSN = mid-systolic notching of the VTI Doppler signal) significantly improves accuracy of PoPH screening compared to ePASP.

Fully Automated Echocardiogram Interpretation in Clinical Practice.

Background: Automated cardiac image interpretation has the potential to transform clinical practice in multiple ways, including enabling serial assessment of cardiac function by nonexperts in primary care and rural settings. We hypothesized that advances in computer vision could enable building a fully automated, scalable analysis pipeline for echocardiogram interpretation, including (1) view identification, (2) image segmentation, (3) quantification of structure and function, and (4) disease detection.

Methods: Using 14 035 echocardiograms spanning a 10-year period, we trained and evaluated convolutional neural network models for multiple tasks, including automated identification of 23 viewpoints and segmentation of cardiac chambers across 5 common views.