Citations

Current management of patients with congenital heart disease has increased their survival into adulthood. This is accompanied by potential cardiac complications, including pulmonary hypertension associated with congenital heart disease (PAH-CHD). PAH-CHD constitutes a challenging subgroup of pulmonary hypertension and requires expert management to improve quality of life and prognosis. Novel agents have shown a significant improvement in morbidity and mortality in patients with pulmonary arterial hypertension. However, the long-term effects of these medications on PAH-CHD patients remain somewhat uncertain, necessitating treatment plans largely founded on the clinical experience of the healthcare providers. The aim of this review is to summarize the current evidence and future perspectives regarding treatment strategies for PAH-CHD to help better guide management of this complex disease.

Case description: A 67 year old female presented for annual review to the transplant clinic 4 years post orthotopic heart transplant for nonischemic dilated cardiomyopathy. She was asymptomatic. Her medical history included hypothyroidism, hypertension, osteoporosis, restless leg syndrome and calcineurin inhibitor related complications - CKD 3b, impaired glucose tolerance and a left partial glossectomy with neck dissection for stage 3 SCC of the left lateral tongue. Medications included aspirin, atorvastatin, prednisolone, tacrolimus, septrin and ropinirole. Family history was significant for heart failure in her father. She was a nonsmoker and did not consume alcohol. Physical examination was unremarkable. Diagnostic tests are shown below. Discussion: Apical hypertrophic cardiomyopathy (ApHCM) has rarely been described in post cardiac transplant populations. Characterized by increased left ventricular apical wall thickness, it results in a ‘spade-like’ appearance on imaging and is associated with marked T wave inversion on ECG. ApHCM is associated with progression to heart failure, apical aneurysm, ventricular arrhythmias and increased mortality rates. Patients may be asymptomatic at diagnosis. Regarding screening, criteria exist for the selection of donor hearts pre transplant with caution exercised if LVH >13mm. Causes of non HCM hypertrophy in this population include calcineurin inhibitors, hypertension, obesity and graft versus host disease. Data for treatment for ApHCM is lacking however it follows the path of classical HCM, involving the use of beta and calcium channel blockers to reduce demand ischemia and management of sequelae.

Introduction: Exposure to high altitude results in hypobaric hypoxia, leading to physiological changes in the cardiovascular system that may result in dyspnea. Hypoxic simulation testing (HSTs) simulates changes in physiology that occur at a specific altitude. Hypothesis: The use of transthoracic echocardiography (TTE) during HST can detect the raise in right-sided pressures revealing underlying causes of high-altitude dyspnea. Methods: We performed a prospective observational study of consecutive patients with unexplained dyspnea at high altitude who were referred to an aerospace medicine program at a single institution between August 2021 and March 2023. Reduced FiO 2 was administered for 20 minutes to simulate altitude levels specific to patients’ history. TTE images were obtained at baseline and during peak hypoxia to evaluate right ventricular (RV) function, RV systolic pressure, and any possible shunts. Result: The study included 27 patients, with a mean age of 64.7 ±14.4 years and 14 (51.9%) females. No significant abnormalities were seen on baseline TTE and no significant differences in blood pressure and heart rate between baseline and hypoxia simulation were detected. Notably, RV systolic pressure increased at peak hypoxia, while RV systolic function declined as shown by a decrease in S’ wave and TAPSE ( Figure 1 ). Additionally, right to left shunts were present in 19 (70.4%) patients. Of these, four patients (21.1%) had shunts present at baseline with no changes at peak hypoxia, while the severity of shunts increased at peak hypoxia in eight cases (42.1%) and the shunts were only evident during hypoxia in seven patients (36.8%). Conclusion: TTE during HST provides valuable information by revealing the presence of symptomatic, sustained shunts and confirming the decline in RV hemodynamics explaining dyspnea at altitude. Further studies are necessary to establish the optimal clinical role of this physiologic method.

Abstract Introduction Lipoprotein(a) [Lp(a)] is associated with an increased incidence of aortic stenosis. Bioprosthetic aortic valve degeneration and native aortic stenosis share similar pathological mechanisms. Evidence regarding the role of serum Lp(a) concentrations in bioprosthetic aortic valve degeneration is lacking. Purpose To evaluate the association between serum Lp(a) concentrations and bioprosthetic aortic valve degeneration. Methods In this retrospective multicenter study, consecutive patients who underwent a bioprosthetic aortic valve replacement between Jan-2010 and Dec-2020 and had a preoperatory serum Lp(a) measurement were included. A baseline transthoracic echocardiography (TTE) was performed following the aortic valve replacement and a follow-up TTE was performed at least 24 months after the baseline study to determine the presence of bioprosthetic valve degeneration. Significant degeneration was defined as: (a) an increase >10 mmHg in mean bioprosthetic aortic valve gradient from baseline status + a decrease in effective orifice area + a decrease in Doppler velocity index + exclusion of clinically thrombotic leaflet thickening, OR (b) new moderate or severe prosthetic aortic regurgitation (if the main component was periprosthetic, then it was not considered). Lp(a) concentrations were compared between patients with and without degeneration and regression analysis was conducted to investigate the association between bioprosthetic valve degeneration and Lp(a) levels. Results In total, 211 cases were included (mean age 74.1 ±9.4 years, 72.0% males, 29.9% transcatheter aortic valve replacements) (Figure 1). Median time between baseline and follow-up TTE was 5.0 (IQR 3.7) years. Bioprostheses degeneration was observed in 33 (15.6%) patients at follow-up. Median serum levels of Lp(a) were significantly higher in the patients affected by degeneration versus non-affected cases (50.0 vs 15.7 mg/dl, p=0.003). In the regression analysis, high Lp(a) levels (≥30 mg/dl) were associated with degeneration both in a univariate analysis (OR 4.8, 95%CI 2.2-10.9, p<0.001) and multivariate analysis adjusted by other risk factors for bioprostheses degeneration (age, sex, hypertension, smoking, patient prosthesis mismatch, creatinine levels, and body surface area) (OR 5.2, 95%CI 2.1-12.8, p<0.001). Conclusion Serum Lp(a) concentrations seem to be a risk factor for bioprosthetic aortic valve degeneration (Figure 2). There is an increasing need to accurately predict bioprosthetic aortic valve degeneration and to develop novel methods and treatments to increase their durability. Prospective studies are needed to confirm these findings and to investigate whether lowering Lp(a) could slow bioprostheses degradation.Population characteristicsLp(a) and bioprostheses degeneration

Abstract Background Cardiac masses encompass a wide differential including primary and secondary malignancies and can present with a variety of symptoms, many of which are non-specific. Early identification and classification are important, particularly for cardiac malignancies such as sarcomas as these are aggressive tumours with exceptionally poor prognoses when metastases are present at diagnosis. Case summary We report two cases of patients who presented with dyspnoea and were diagnosed with cardiac sarcomas; the former a primary sarcoma (undifferentiated pleomorphic subtype) and the latter a secondary sarcoma (round cell myxoid liposarcoma) that serve as comparisons for presentation and management of different types of this disease. Computed Tomography (CT) and echocardiography imaging findings are demonstrated showing the typical location and morphology of each subtype. Discussion Cardiac sarcomas are the most common primary cardiac malignancy, of which undifferentiated pleomorphic sarcoma is a common subtype. Undifferentiated pleomorphic sarcomas are aggressive, have a tendency to arise in the left atrium, and can appear similar to benign cardiac masses. Round cell myxoid liposarcomas by contrast are rare causes of secondary cardiac malignancies, metastasizing to the heart from soft tissues. Both diagnoses carry poor prognoses and although rare, are important to recognize as timely intervention with surgery, radiotherapy, and consideration of chemotherapy is key to maximizing survival.

Chest radiography (CXR) is the most frequently performed radiological test worldwide because of its wide availability, non-invasive nature, and low cost. The ability of CXR to diagnose cardiovascular diseases, give insight into cardiac function, and predict cardiovascular events is often underutilized, not clearly understood, and affected by inter- and intra-observer variability. Therefore, more sophisticated tests are generally needed to assess cardiovascular diseases. Considering the sustained increase in the incidence of cardiovascular diseases, it is critical to find accessible, fast, and reproducible tests to help diagnose these frequent conditions. The expanded focus on the application of artificial intelligence (AI) with respect to diagnostic cardiovascular imaging has also been applied to CXR, with several publications suggesting that AI models can be trained to detect cardiovascular conditions by identifying features in the CXR. Multiple models have been developed to predict mortality, cardiovascular morphology and function, coronary artery disease, valvular heart diseases, aortic diseases, arrhythmias, pulmonary hypertension, and heart failure. The available evidence demonstrates that the use of AI-based tools applied to CXR for the diagnosis of cardiovascular conditions and prognostication has the potential to transform clinical care. AI-analyzed CXRs could be utilized in the future as a complimentary, easy-to-apply technology to improve diagnosis and risk stratification for cardiovascular diseases. Such advances will likely help better target more advanced investigations, which may reduce the burden of testing in some cases, as well as better identify higher-risk patients who would benefit from earlier, dedicated, and comprehensive cardiovascular evaluation.

Immune checkpoint inhibitors (ICIs) induce profound benefits in cancer patients with mismatch repair gene mutations or high levels of microsatellite instability. Herein, we present a case of a patient with history of Muir-Torre/Lynch syndrome and metastatic gastric adenocarcinoma in the presence of an MSH2 gene mutation. The patient was initially treated with a PD-1 inhibitor, pembrolizumab, but developed grade 4 myocarditis requiring treatment with infliximab and a prolonged steroid taper. Following discontinuation of pembrolizumab, surveillance testing showed no radiographic or endoscopic evidence of progression for 7 months, until biopsy results from a repeat upper endoscopy indicated local disease recurrence. The patient was subsequently rechallenged with another PD-1 inhibitor, nivolumab, at a 50% dose reduction without recurrent adverse events and eventually achieved a complete response after 13 cycles. This case highlights the relative importance of considering careful rechallenge with ICI therapy in patients with microsatellite instability–high malignancies and a high risk of severe adverse events.

Cardiac structural and valve interventions have remained surgical procedures for several decades. The ability to directly visualize the region of interest during surgery made imaging of these structures pre- and postsurgery a secondary tool to compliment surgical visualization. The last two decades, however, have seen rapid advances in catheter-based percutaneous structural heart interventions (SHIs). Due to the “blind” nature of these interventions, imaging plays a crucial role in the success of these procedures. Fluoroscopy is used universally in all percutaneous cardiac SHIs and helps primarily in the visualization of catheters and devices. However, success of these procedures requires visualization of intracardiac soft tissue structures. Due to its portable nature and rapid ability to show cardiac structures online, transesophageal echocardiography (TEE) has become an integral tool for guidance for all percutaneous SHI. Transcatheter aortic valve replacement—one of the earliest catheter-based procedures—while initially dependent on TEE, has largely been replaced by preprocedural cardiac CT for accurate assessment of valve sizing. Developments in echocardiography now allow live three-dimensional (3D) visualization of cardiac structures mimicking surgical anatomy during TEE. Besides showing actual 3D intracardiac structures, 3D-TEE allows visualization of the interaction of intracardiac catheters and devices with soft tissue cardiac structures, thereby becoming a “second pair of eyes” for the operator. Real-time 3D-TEE now plays an important role complementing multiplane two dimensional and biplane TEE during such interventions. In this review, we discuss the incremental role of 3D-TEE during various SHIs performed today.

Objectives Lipoprotein(a) (Lp(a)) is associated with an increased incidence of native aortic stenosis, which shares similar pathological mechanisms with bioprosthetic aortic valve (bAV) degeneration. However, evidence regarding the role of Lp(a) concentrations in bAV degeneration is lacking. This study aims to evaluate the association between Lp(a) concentrations and bAV degeneration. Methods In this retrospective multicentre study, patients who underwent a bAV replacement between 1 January 2010 and 31 December 2020 and had a Lp(a) measurement were included. Echocardiography follow-up was performed to determine the presence of bioprosthetic valve degeneration, which was defined as an increase >10 mm Hg in mean gradient from baseline with concomitant decrease in effective orifice area and Doppler Velocity Index, or new moderate/severe prosthetic regurgitation. Levels of Lp(a) were compared between patients with and without degeneration and Cox regression analysis was performed to investigate the association between Lp(a) levels and bioprosthetic valve degeneration. Results In total, 210 cases were included (mean age 74.1±9.4 years, 72.4% males). Median time between baseline and follow-up echocardiography was 4.4 (IQR 3.7) years. Bioprostheses degeneration was observed in 33 (15.7%) patients at follow-up. Median serum levels of Lp(a) were significantly higher in patients affected by degeneration versus non-affected cases: 50.0 (IQR 72.0) vs 15.6 (IQR 48.6) mg/dL, p=0.002. In the regression analysis, high Lp(a) levels (≥30 mg/dL) were associated with degeneration both in a univariable analysis (HR 3.6, 95% CI 1.7 to 7.6, p=0.001) and multivariable analysis adjusted by other risk factors for bioprostheses degeneration (HR 4.4, 95% CI 1.9 to 10.4, p=0.001). Conclusions High serum Lp(a) is associated with bAV degeneration. Prospective studies are needed to confirm these findings and to investigate whether lowering Lp(a) levels could slow bioprostheses degradation.

Lipoprotein(a) [Lp(a)] is a lipid molecule with atherogenic, inflammatory, thrombotic, and antifibrinolytic effects, whose concentrations are predominantly genetically determined. The association between Lp(a) and cardiovascular diseases (CVDs) has been well-established in numerous studies, and the ability to measure Lp(a) levels is widely available in the community. As such, there has been increasing interest in Lp(a) as a therapeutic target for the prevention of CVD. The impact of the currently available lipid-modifying agents on Lp(a) is modest and heterogeneous, except for the monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), which demonstrated a significant reduction in Lp(a) levels. However, the absolute reduction in Lp(a) to significantly decrease CVD outcomes has not been definitely established, and the magnitude of the effect of PCSK9i seems insufficient to directly reduce the Lp(a)-related CVD risk. Therefore, emerging therapies are being developed that specifically aim to lower Lp(a) levels and the risk of CVD, including RNA interference (RNAi) agents, which have the capacity for temporary and reversible downregulation of gene expression. This review article aims to summarize the effects of Lp(a) on CVD and to evaluate the available evidence on established and emerging therapies targeting Lp(a) levels, focusing on the potential reduction of CVD risk attributable to Lp(a) concentrations.