Faculty Bibliography

Although adoption of noninvasive cardiac scintigraphy has transformed the diagnosis of transthyretin cardiac amyloidosis, significant challenges remain, particularly in indeterminate scintigraphy findings, light chain amyloidosis, and rare amyloid subtypes. Part I reviewed the technical foundations and key endpoints of cardiac magnetic resonance (CMR). In this Part II, we review evidence supporting the role of CMR in diagnosis, including differentiation from other causes of left ventricular wall thickening, and subtyping, particularly in early disease. We also summarize the prognostic value of CMR-derived measures. Lastly, we discuss the emerging role of serial CMR in monitoring treatment response in light chain cardiac amyloidosis.

Amyloidosis is a systemic disease characterized by the extracellular deposition of the misfolded proteins resulting in organ dysfunction, frequently the heart. Cardiac amyloidosis is an underrecognized cause of heart failure which carries significant morbidity and mortality when its diagnosis is delayed. Cardiac magnetic resonance (CMR) imaging has emerged as critical technique in diagnosis of cardiac amyloidosis through its unique ability to non-invasively measure myocardial tissue characteristics and changes in extracellular volume. In turn, CMR allows differential diagnosis, early detection, and precise characterization of amyloid disease pathology. This review focuses on the technical foundations of CMR relevant to cardiac amyloidosis.

BACKGROUND:Cardiogenic shock (CS) is a common complication of acute coronary syndrome (ACS) and is associated with significant morbidity and mortality. Revascularization has been shown to reduce mortality in ACS-CS. Patients with cancer are at high risk of ACS and CS. However, patients with cancer are often undertreated with invasive procedures and outcomes of patients with cancer and ACS-CS have not been thoroughly characterized. METHODS:Patients with ACS-CS from 2014 to 2020 with and without cancer were identified using the National Readmission Database (NRD). Primary outcome was death at 90-days. Secondary outcomes were 90-day cardiovascular (CV) and bleeding readmissions, and index hospitalization major bleeding and thrombotic complications. Patients with cancer were compared to patients without cancer using multivariable logistic and Cox proportional hazards regression. Temporal trends in revascularization among patients with and without cancer were examined. Effect of revascularization among patients with cancer and ACS-CS was assessed using propensity score weighting (PSW). RESULTS:A total of 140,205 patients were identified, of whom 6118 (4.4 %) with cancer were identified. Patients with cancer were less likely to undergo percutaneous coronary intervention (45.5 % vs 53.5 %) or be managed with mechanical circulatory support (36.6 % vs 46.0 %). After multivariable logistic regression, there was no difference in primary outcome (adjusted OR 0.98, 95 % CI 0.92-1.06) but patients with cancer had higher risk of 90-day CV (HR 1.11, 95 % CI 1.01-1.22) and bleeding readmissions (HR 1.39, 95 % CI 1.10-1.76). Among patients with cancer and ACS-CS, revascularization was associated with lower primary outcome (OR 0.54, 95 % CI 0.50-0.58) and 90-day CV readmission (HR 0.68, 95 % CI 0.59-0.77) after PSW. CONCLUSIONS:Among patients with ACS-CS, patients with cancer have similar 90-day death but higher risk of 90-day CV and bleeding readmissions. Additionally, revascularization was associated with improved outcomes among patients with cancer and ACS-CS. Further studies are needed to optimize patient selection for invasive management among patients with cancer.

BACKGROUND:We present the case of a 74-year-old woman diagnosed with obstructive hypertrophic cardiomyopathy. CASE SUMMARY/METHODS:Amyloidosis was initially considered because she was genotype positive in the transthyretin gene. However, because of 2 negative 99m technetium pyrophosphate radionuclide scans, this diagnosis was considered unlikely, and endomyocardial biopsy was deferred. She had an adverse response to all attempted medical therapies for her left ventricular outflow tract obstruction and ultimately underwent surgical myectomy. Surgical pathology revealed transthyretin (TTR) amyloidosis. DISCUSSION/CONCLUSIONS:This case highlights the limitations of diagnostic testing and reinforces the consideration of more invasive procedures to determine the true underlying cause of disease. This helps clinicians provide the most advanced level of treatment available. TAKE-HOME MESSAGES/CONCLUSIONS:TTR amyloidosis can mimic hypertrophic cardiomyopathy with left ventricular outflow tract obstruction. 99m Technetium pyrophosphate scans are useful to investigate the presence of TTR amyloid, but if suspicion persists despite negative testing, it is reasonable to perform an endomyocardial biopsy.

Patients with myeloproliferative neoplasms (MPNs) are at increased risk for cardiovascular disease. Although thrombosis is a well-recognized complication, emerging evidence indicates that nonthrombotic conditions, including heart failure (HF) and pulmonary hypertension (PH), are also prevalent and associated with adverse cardiovascular and hematologic outcomes. Clinical and preclinical data suggest a shared pathophysiology linking MPNs to the development and progression of cardiomyopathy, HF, and both precapillary and postcapillary PH. Recent studies further support a bidirectional relationship, in which HF and PH are associated with hematologic progression and vice versa. Elucidating the mechanisms underlying these interactions may uncover novel therapeutic targets and inform clinical management. Here, the authors review the pathophysiology and impact of HF and PH in patients with MPNs.

BACKGROUND:Acute decompensated heart failure (HF) can progress to cardiogenic shock, and patients with cancer are at an increased risk of HF compared to patients without cancer. However, limited data exist on outcomes of patients admitted for HF-related cardiogenic shock (HF-CS) with cancer versus without cancer. METHODS:Adult patients admitted for HF-CS between 2014-2020 were identified using the National Readmission Database. Propensity score matching (PSM) was used to match 1 patient with cancer to 10 patients without cancer. Primary outcomes were in-hospital death, major bleeding, and thrombotic complications. Exploratory outcomes were 90-day readmission rates among patients who survived initial hospitalization. Temporal trends were also explored. RESULTS:Of 137,316 admissions for HF-CS, 7,306 (5.3%) had active cancer. After PSM, patients with cancer had increased odds of in-hospital death (OR 1.12, 95% CI 1.06 - 1.18), thrombotic complications (OR 1.12, 95% CI 1.03 - 1.21), and major bleeding (OR 1.23, 95% CI 1.17 - 1.31) compared to patients without cancer, with risks differing by cancer type. In exploratory analyses, rates of readmission were similar for patients with and without cancer. From 2014-2020, patients with cancer had no significant change in in-hospital mortality (ptrend = 0.43), while patients without cancer had decreased mortality over time (ptrend < 0.001). CONCLUSIONS:Among patients admitted for HF-CS, patients with cancer are at increased risk of in-hospital death, thrombotic complications, and major bleeding compared to patients without cancer. Future studies are needed to guide nuanced evaluation and management of this population to improve outcomes.

INTRODUCTION/BACKGROUND:Patients with congenital heart disease (CHD) are at increased risk of cancer. In patients with CHD and advanced heart failure, isolated heart transplantation (HT) can be considered. In the overall HT population, immunosuppression after HT increases the risk of post-transplant malignancy (PTM). However, cancer outcomes among adult HT patients with CHD have not been investigated. METHODS:Patients aged ≥ 18 years who received HT between January 1, 2010 and December 31, 2021 were identified using the United Network for Organ Sharing (UNOS) registry. Patients with CHD were compared to those without. T primary outcome was a composite outcome of PTM or death due to malignancy. Multivariable Fine-Gray competing-risk regression was used to estimate the subhazard ratio (SHR) of primary and secondary outcomes. RESULTS:Of the total of 29717 patients with HT were included, 1017 (3.4%) had CHD. Patients with CHD were younger, more likely to be female, and have had prior cardiac surgery. After multivariable competing-risk regression, CHD was associated with a higher risk of the primary outcome (SHR 1.43, 95% CI 1.15-1.80). Among patients who developed PTM, the median time to diagnosis of first PTM (median 36 vs. 46 months, p = 0.027) was shorter in patients with CHD. Among patients with CHD, survival after PTM was significantly lower compared with patients without malignancy (HR 3.32, 95% CI 2.03-5.43). CONCLUSIONS:Among adult patients with HT, CHD was associated with an increased risk of PTM. Further investigation is warranted to identify risk factors and screening strategies for malignancy in this patient population.

Heart failure (HF) in patients with cancer is associated with high morbidity and mortality. The success of cancer therapy has resulted in an exponential rise in the population of cancer survivors, however cardiovascular disease (CVD) is now a major life limiting condition more than 5 years after cancer diagnosis [Sturgeon, Deng, Bluethmann, et al 40(48):3889-3897, 2019]. Prevention and early detection of CVD, including cardiomyopathy (CM) and HF is of paramount importance. The European Society of Cardiology (ESC) published guidelines on Cardio-Oncology (CO) [Lyon, López-Fernández, Couch, et al 43(41):4229-4361, 2022] detailing cardiovascular (CV) risk stratification, prevention, monitoring, diagnosis, and treatment throughout the course and following completion of cancer therapy. Here we utilize a case to summarize aspects of the ESC guideline relevant to HF clinicians, with a focus on risk stratification, early detection, prevention of CM and HF, and the role for guideline directed medical therapy in patients with cancer.

Gastrointestinal cancers are a heterogenous group of cancers that share common risk factors with cardiovascular disease. Therapy for gastrointestinal cancers have improved cancer-specific outcomes at the cost of cardiotoxicity. The most common cardiotoxic therapies utilized in gastrointestinal cancers include conventional chemotherapy (including fluoropyrimidines and anthracyclines), targeted therapies including anti-vascular endothelial growth factor (VEGF) therapy and tyrosine kinase inhibitors (TKI), and immunotherapy. It is important for clinicians managing patients with gastrointestinal cancers to be aware of potential cardiotoxicity associated with these agents.

The prevalence of amyloidosis has been increasing, driven by a combination of improved awareness, evolution of diagnostic pathways, and effective treatment options for both transthyretin and light chain amyloidosis. Due to the complexity of amyloidosis, centralised expert providers with experience in delineating the nuances of confirmatory diagnosis and management may be beneficial. There are many potential benefits of a centre of excellence designation for the treatment of amyloidosis including recognition of institutions that have been leading the way for the optimal treatment of this condition, establishing the expectations for any centre who is engaging in the treatment of amyloidosis and developing cooperative groups to allow more effective research in this disease space. Standardising the expectations and criteria for these centres is essential for ensuring the highest quality of clinical care and community education. In order to define what components are necessary for an effective centre of excellence for the treatment of amyloidosis, we prepared a survey in cooperation with a multidisciplinary panel of amyloidosis experts representing an international consortium. The purpose of this position statement is to identify the essential elements necessary for highly effective clinical care and to develop a general standard with which practices or institutions could be recognised as a centre of excellence.