Cardiac Complications in the Adult Bone Marrow Transplant Patient
CURRENT ONCOLOGY REPORTS
2019; 21 (3): 28
A Changing Landscape of Mortality for Systemic Light Chain Amyloidosis.
JACC. Heart failure
Due to advancements in oncologic treatment strategies and techniques, the number of survivors who have undergone hematopoetic stem cell transplant (HCT) continues to increase in the United States; this number is projected to reach 502,000 by the year 2030. There is significant interest within the field of cardio-oncology to identify cardiotoxicity and cardiovascular disease in the HCT population. Epidemiologic studies analyzing both short- and long-term cardiovascular effects, risk stratification modeling, cardioprotective strategies, and expert consensus documents for cardiotoxicity surveillance recommendations are reviewed.Patients who have undergone HCT are at increased risk of cardiovascular events and mortality compared to matched controls. The type of cardiotoxicity and the incidence rates vary based on specific therapeutic regimens and pre-existing cardiovascular risk factors. Life-threatening cardiotoxicity can present during HCT as acute heart failure, arrhythmias, pericardial tamponade, or cardiac arrest; or it can present late after treatment as cardiomyopathy, ischemic heart disease, vascular disease, stroke, or comorbid conditions, such as hypertension and diabetes mellitus that are associated with cardiac events. HCT is associated with excess cardiovascular risk partially due to exposure to cardiotoxic chemotherapy and radiation, as well as indirect and direct detrimental effects on cardiovascular reserve. This review discusses the epidemiology and the known cardiotoxic effects of historical chemoradiation agents in addition to newer targeted therapies. Recent expert consensus statements from cardiology and hematology/oncology societies are reviewed in regard to risk stratification of the cancer patient based on the type of treatments. Finally, gaps in knowledge are identified with proposed avenues of research that will allow for more accurate risk assessment, prediction, and potential treatment of the HCT patient in attenuating the risk of developing both short- and long-term cardiovascular comorbidities.
View details for DOI 10.1007/s11912-019-0774-6
View details for Web of Science ID 000460117600001
View details for PubMedID 30826891
Improving risk stratification in heart failure with preserved ejection fraction by combining two validated risk scores.
2019; 6 (1): e000961
The purpose of this study was to address the overall trends in mortality since the adoption of modern therapies for treatment of systemic amyloidosis, and to reconsider the prognostic significance of individual components of the current staging system.Systemic light chain (AL) amyloidosis involves deposition of immunoglobulin light chains in organs throughout the body and is known to have the highest mortality when significant cardiac involvement is present. Survival has historically been poor but may be improving as systemic therapies continue to advance. This study assesses whether recent advancements in light chain directed therapy have led to improved survival in patients with systemic AL amyloidosis.We reviewed all cases of patients who were evaluated for a new diagnosis of AL amyloidosis at the Stanford Amyloid Center between 2009 and 2016. Patients' stage at diagnosis was determined according to the most commonly used staging system. Clinical data, overall survival from diagnosis, and the independent influence of each component of the staging system were analyzed.At total of 194 patients were identified with a new diagnosis of systemic AL amyloidosis. Median overall survival was 59 months and 6 months for stage 3 and 4 patients, respectively. Median overall survival was not reached in stage 1 and 2 groups, as survival was >50% by the end of the study. Mean overall survival was 118 months, 76 months, 64 months, and 27 months in Stages 1, 2, 3, and 4 patients, respectively. Although N-terminal pro-B-type natriuretic peptide and troponin I concentrations had large effects on prognosis, differences in serum free light chains (dFLC) on initial staging laboratory results ?18 mg/dl, part of the current staging system, did not contribute significantly to prognosis for values ?5 mg/dl.Survival for patients with systemic AL amyloidosis has improved for patients at all stages of disease in the present era of rapid advancements in light chain-reducing therapies. Cardiac biomarkers at diagnosis, but not baseline dFLC ?18 mg/dl, continue to provide important prognostic information.
View details for DOI 10.1016/j.jchf.2019.07.007
View details for PubMedID 31606365
National Outcomes in Hospitalized Patients With Cancer and Comorbid Heart Failure.
Journal of cardiac failure
Introduction: The Intermountain Risk Score (IMRS) was developed and validated to predict short-term and long-term mortality in hospitalised patients using demographics and commonly available laboratory data. In this study, we sought to determine whether the IMRS also predicts all-cause mortality in patients hospitalised with heart failure with preserved ejection fraction (HFpEF) and whether it is complementary to the Get with the Guidelines Heart Failure (GWTG-HF) risk score or N-terminal pro-B-type natriuretic peptide (NT-proBNP).Methods and results: We used the Stanford Translational Research Integrated Database Environment to identify 3847 adult patients with a diagnosis of HFpEF between January 1998 and December 2016. Of these, 580 were hospitalised with a primary diagnosis of acute HFpEF. Mean age was 76±16 years, the majority being female (58%), with a high prevalence of diabetes mellitus (36%) and a history of coronary artery disease (60%). Over a median follow-up of 2.0 years, 140 (24%) patients died. On multivariable analysis, the IMRS and GWTG-HF risk score were independently associated with all-cause mortality (standardised HRs IMRS (1.55 (95% CI 1.27 to 1.93)); GWTG-HF (1.60 (95% CI 1.27 to 2.01))). Combining the two scores, improved the net reclassification over GWTG-HF alone by 36.2%. In patients with available NT-proBNP (n=341), NT-proBNP improved the net reclassification of each score by 46.2% (IMRS) and 36.3% (GWTG-HF).Conclusion: IMRS and GWTG-HF risk scores, along with NT-proBNP, play a complementary role in predicting outcome in patients hospitalised with HFpEF.
View details for DOI 10.1136/openhrt-2018-000961
View details for PubMedID 31217994
Natural history of myocardial deformation in children, adolescents, and young adults exposed to anthracyclines: Systematic review and meta-analysis
ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES
2018; 35 (7): 922?34
Heart failure (HF) and cancer are a significant cause of morbidity and mortality in the US. Due to overlapping risk factors, these two conditions often coexist.We sought to describe the national burden of HF for hospitalized patients with cancer. We identified adults admitted with a primary oncologic diagnosis in 2014 included in the National Inpatient Sample (NIS). Patient hospitalizations were divided based on presence or absence of comorbid HF. Primary outcomes included cost, length of stay (LOS), and inpatient mortality. Logistic regression analysis with cluster adjustment was performed to determine predictors of inpatient mortality.There were 834,900 admissions for a primary oncologic diagnosis in patients without comorbid HF, and 64,740 (7.2%) admissions for patients with comorbid HF. Patients with HF were on average older and had more comorbidities. Patients with HF had significantly higher mean hospitalization cost ($22,571 vs $20,234, p-value <0.001), age-standardized LOS (12.7 vs 8.2 days, p-value <0.001), and age-standardized inpatient mortality (12.2% vs 4.5%, p-value <0.001). Presence of HF predicted inpatient mortality after adjusting for age, race, insurance payer, and comorbidity index (OR 1.12, 95% CI 1.04-20, p-value = 0.002).Patients with cancer hospitalized with comorbid HF represent a high-risk population with increased costs and high inpatient mortality rates. More data is needed to determine what screening and treatment measures may improve outcomes.
View details for DOI 10.1016/j.cardfail.2019.02.007
View details for PubMedID 30769035
Arterial Thrombosis in Patients with Cancer.
Current treatment options in cardiovascular medicine
2018; 20 (5): 40
Anthracyclines are widely used to treat solid and hematologic malignancies, but are known to cause cardiotoxicity. As more childhood cancer survivors reach adulthood due to improvements in oncologic treatments, they become susceptible to late and progressive anthracycline-induced cardiotoxicity. Nonetheless, diagnostic criteria for early detection of cardiac dysfunction are not well defined in children, adolescent, and young adults (CAYA, ages 1-40 years). We present a natural history of the changes in myocardial deformation in CAYA patients after anthracycline therapy.We performed a literature review search between 2001 and 2016 using PubMed with the following search terms: strain (or deformation), torsion (or twist), children (or adolescent or young adult), cardiotoxicity (or dysfunction), and anthracyclines (or doxorubicin). A total of 23 articles were reviewed. Fourteen articles were incorporated in the meta-analysis.Strain abnormalities are observed at both short-term and long-term follow-up. Global longitudinal strain (GLS) abnormalities are common during or early after chemotherapy, whereas changes in global circumferential strain (GCS) are more significant and consistent on long-term follow-up. Although global radial strain and torsional parameters are also often abnormal late after chemotherapy, there are few studies evaluating these parameters.There are significant abnormalities in GLS and GCS following anthracycline therapy acutely and late after treatment. The prognostic value of these strain abnormalities warrants further investigation.
View details for DOI 10.1111/echo.13871
View details for Web of Science ID 000437763900003
View details for PubMedID 29603386
View details for PubMedCentralID PMC6544758
Challenging the complementarity of different metrics of left atrial function: insight from a cardiomyopathy-based study
EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING
2017; 18 (10): 1153?62
Cardiac Amyloidosis: Diagnosis and Treatment Strategies
CURRENT ONCOLOGY REPORTS
2017; 19 (7): 46
Cancer is a common cause of morbidity and mortality in the USA. While the association between venous thrombosis and malignancy is well established, arterial thrombosis has more recently been recognized as a serious complication of cancer and certain chemotherapeutic agents. This review aims to summarize the most recent literature regarding the incidence and risk factors for cancer-related arterial thrombosis, understand the pathophysiologic mechanisms of thrombosis, and highlight the specific diagnostic and treatment considerations relevant to cancer patients.Based on a recent study looking at the Surveillance, Epidemiology, and End Results (SEER) database, the incidence of arterial thromboembolic events (ATEs) in patients with cancer at 6 months is 4.7%; the presence of an ATE is predictive of worse outcomes. Certain drugs such as platinum-based agents, vascular endothelial growth factor inhibitors, tyrosine kinase inhibitors, and taxanes have been associated with high rates of ATEs. Increased platelet reactivity appears crucial to development of arterial thrombosis in cancer patients. Cancer patients have an increased risk of arterial thrombosis that is likely due to both a cancer-associated procoagulant state as well as the adverse effects of certain chemotherapeutic agents. Treatment of arterial thromboembolism in cancer patients typically requires a multidisciplinary approach in part due to high rates of thrombocytopenia and stent thrombosis in the setting of percutaneous interventions. More studies are needed to investigate optimal prophylaxis, surveillance strategies, and treatments of cancer-related arterial thromboembolic disease.
View details for DOI 10.1007/s11936-018-0635-x
View details for PubMedID 29627870
Functional Cardiac Recovery and Hematologic Response to Chemotherapy in Patients With Light-Chain Amyloidosis (from the Stanford University Amyloidosis Registry).
The American journal of cardiology
2017; 120 (8): 1381?86
Cardiac amyloidosis in the United States is most often due to myocardial infiltration by immunoglobulin protein, such as in AL amyloidosis, or by the protein transthyretin, such as in hereditary and senile amyloidosis. Cardiac amyloidosis often portends a poor prognosis especially in patients with systemic AL amyloidosis. Despite better understanding of the pathophysiology of amyloid, many patients are still diagnosed late in the disease course. This review investigates the current understanding and new research on the diagnosis and treatment strategies in patients with cardiac amyloidosis. Myocardial amyloid infiltration distribution occurs in a variety of patterns. Structural and functional changes on echocardiography can suggest presence of amyloid, but CMR and nuclear imaging provide important complementary information on amyloid burden and the amyloid subtype, respectively. While for AL amyloid, treatment success largely depends on early diagnosis, for ATTR amyloid, new investigational agents that reduce production of transthyretin protein may have significant impact on clinical outcomes. Advancements in the non-invasive diagnostic detection and improvements in early disease recognition will undoubtedly facilitate a larger proportion of patients to receive early therapy when it is most effective.
View details for DOI 10.1007/s11912-017-0607-4
View details for Web of Science ID 000405097700003
View details for PubMedID 28528458
Challenging the complementarity of different metrics of left atrial function: insight from a cardiomyopathy-based study.
European heart journal cardiovascular Imaging
Cardiac involvement is common in patients with light-chain (AL) amyloidosis and portends a poor prognosis, although little is known about the changes in cardiac mechanics after chemotherapy. We sought to explore the relation between amyloidosis staging and baseline cardiac mechanics and to investigate short-term changes in cardiac mechanics after chemotherapy. We identified 41 consecutive patients from the Stanford Amyloid Center who had echocardiograms and free light-chain values before and after chemotherapy, along with 40 age- and gender-matched controls. Echocardiographic assessment included left ventricular global longitudinal strain, E/e' ratio, and left atrial (LA) stiffness. Hematologic response to chemotherapy was defined as ?50% reduction in the difference between the involved and the uninvolved free light chain (dFLC). The mean age was 66.9?±?8.4 years and 66% were men. Before chemotherapy, global longitudinal strain, E/e' ratio, and LA stiffness were impaired in patients with amyloidosis compared with controls, and the severity of impairment worsened with advanced staging. After chemotherapy, hematologic response was observed in 30 (73%) patients. There was a significant association between the change in dFLC and cardiac function (E/e' ratio: r?=?-0.43, p?=?0.01; LA stiffness: r?=?-0.35, p?=?0.05). There was no significant improvement in cardiac mechanics in patients without a hematologic response to chemotherapy. In conclusion, amyloidosis stage correlated with noninvasive measurements of cardiac mechanics, and improvement in dFLC correlated with cardiac improvement on short-term follow-up echocardiography.
View details for PubMedID 28844519
Regional right ventricular dysfunction in acute pulmonary embolism: relationship with clot burden and biomarker profile
INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING
2016; 32 (3): 389-398
Left ventricular (LV) strain provides incremental values to LV ejection fraction (LVEF) in predicting outcome. We sought to investigate if similar relationship is observed between left atrial (LA) emptying fraction and LA strain.In this study, we selected 50 healthy subjects, 50 patients with dilated, 50 hypertrophic, and 50 infiltrative (light-chain (AL) amyloidosis) cardiomyopathy (CMP). Echocardiographic measures included LVEF and LA emptying fraction as well as LV and LA longitudinal strain (LVLS and LALS). After regression analysis, comparison of least square means of LA strain among aetiologies was performed. Intraclass correlation coefficient (ICC) and coefficient of variation (COV) were used in the assessment of variability and reproducibility of LV and LA metrics. The mean LVLS and all LA metrics were impaired in patients with all CMP compared with healthy subjects. In contrast to the moderate relationship between LVEF and LVLS (r = -0.51, P < 0.001), there was a strong linear relationship between LA emptying fraction and LA strain (r = 0.87, P < 0.001). In multiple regression analysis, total LA strain was associated with LVLS (? = -0.48, P < 0.001), lateral E/e' (? = -0.24, P < 0.001), age (? = -0.21, P < 0.001), and heart rate (? = -0.14, P = 0.02). The least square mean of LA strain adjusted for the parameters was not different among aetiologies (ANOVA P = 0.82). The ICC (>0.77) and COV (<13) were acceptable.In contrast to LV measures, there is a strong linear relationship between volumetric and longitudinal deformation indices of left atrium irrespective of CMP aetiology. Either LA emptying fraction or LA strain could be used as an important parameter in predictive models.
View details for PubMedID 27638850
Regional right ventricular (RV) dysfunction (RRVD) is an echocardiographic feature in acute pulmonary embolism (PE), primarily reported in patients with moderate-to-severe RV dysfunction. This study investigated the clinical importance of RRVD by assessing its relationship with clot burden and biomarkers. We identified consecutive patients admitted to the emergency department between 1999 and 2014 who underwent computed tomographic angiography, echocardiography, and biomarker testing (troponin and NT-proBNP) for suspected acute PE. RRVD was defined as normal excursion of the apex contrasting with hypokinesis of the mid-free wall segment. RV assessment included measurements of ventricular dimensions, fractional area change, free-wall longitudinal strain and tricuspid annular plane systolic excursion. Clot burden was assessed using the modified Miller score. Of 82 patients identified, 51 had acute PE (mean age 66 ± 17 years, 43 % male). No patient had RV myocardial infarction. RRVD was present in 41 % of PEs and absent in all patients without PE. Among patients with PE, 86 % of patients with RRVD had central or multi-lobar PE. Patients with RRVD had higher prevalence of moderate-to-severe RV dilation (81 vs. 30 %, p < 0.01) and dysfunction (86 vs. 23 %, p < 0.01). There was a strong trend for higher troponin level in PE patients with RRVD (38 vs. 13 % in PE patients without RRVD, p = 0.08), while there was no significant difference for NT-proBNP (67 vs. 73 %, p = 0.88). RRVD showed good concordance between readers (87 %). RRVD is associated with an increased clot burden in acute PE and is more prevalent among patients with moderate-to-severe RV enlargement and dysfunction.
View details for DOI 10.1007/s10554-015-0780-1
View details for PubMedID 26428674