Pimprapa Vejpongsa

Prevention of Anthracycline-Induced Cardiotoxicity: Challenges and Opportunities

Anthracycline compounds are major culprits in chemotherapy-induced cardiotoxicity, which is the chief limiting factor in delivering optimal chemotherapy to cancer patients. Although extensive efforts have been devoted to identifying strategies to prevent anthracycline-induced cardiotoxicity, there is little consensus regarding the best approach. Recent advances in basic mechanisms of anthracycline-induced cardiotoxicity provided a unified theory to explain the old reactive-oxygen species hypothesis and identified topoisomerase 2β as the primary molecular target for cardioprotection. This review outlines current strategies for primary and secondary prevention of anthracycline-induced cardiotoxicity resulting from newly recognized molecular mechanisms and identifies knowledge gaps requiring further investigation.

Emerging Paradigms in Cardiomyopathies Associated With Cancer Therapies

The cardiovascular care of cancer patients (cardio-oncology) has emerged as a new discipline in clinical medicine, given recent advances in cancer therapy, and is driven by the cardiovascular complications that occur as a direct result of cancer therapy. Traditional therapies such as anthracyclines and radiation have been recognized for years to have cardiovascular complications. Less expected were the cardiovascular effects of targeted cancer therapies, which were initially thought to be specific to cancer cells and would spare any adverse effects on the heart. Cancers are typically driven by mutations, translocations, or overexpression of protein kinases. The majority of these mutated kinases are tyrosine kinases, though serine/threonine kinases also play key roles in some malignancies. Several agents were developed to target these kinases, but many more are in development. Major successes have been largely restricted to agents targeting human epidermal growth factor receptor-2 (mutated or overexpressed in breast cancer), BCR-ABL (chronic myelogenous leukemia and some cases of acute lymphoblastic leukemia), and c-Kit (gastrointestinal stromal tumor). Other agents targeting more complex malignancies, such as advanced solid tumors, have had successes, but have not extended life to the degree seen with chronic myelogenous leukemia. Years before the first targeted therapy, Judah Folkman correctly proposed that to address solid tumors one had to target the inherent neoangiogenesis. Unfortunately, emerging evidence confirms that angiogenesis inhibitors cause cardiac complications, including hypertension, thrombosis, and heart failure. And therein lies the catch-22. Nevertheless, cardio-oncology has the potential to be transformative as the human cardiomyopathies that arise from targeted therapies can provide insights into the normal function of the heart.

Early readmissions after transcatheter and surgical aortic valve replacement

We aimed to determine and compare the prevalence, and predictors of readmissions after the transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR).

Wrestling With Heart Failure: SUMO-1 to the Rescue

SUMO-1 Gene Transfer Improves Cardiac Function in a Large-Animal Model of Heart Failure Tilemann et al Sci Transl Med . 2013;5:211ra159. A small ubiquitin-like protein was shown to be beneficial to the failing heart through enhancing sarcoplasmic reticulum Ca 2+ ATPase 2a (SERCA2a) stability and activity in a large animal model of heart failure. Dysregulation of calcium cycling in cardiomyocytes has been recognized as a major molecular mechanism of heart failure. SERCA2a plays a pivotal role in regulating calcium homeostasis, and reduction of SERCA2a activity has been recognized as a hallmark of heart failure. Hajjar and his colleagues1 reported that the activity of SERCA2a is regulated by conjugation of small ubiquitin-like modifier-1 (SUMO-1) to SERCA2a. They also demonstrated that SUMO-1 gene delivery can restore SERCA2a expression and activity in the failing heart in a mouse model. Based on these findings, they postulated that SUMO modification (SUMOylation) is a critical regulator of SERCA2a function, which led to the design of SUMO-1 gene therapy in a swine ischemia–reperfusion heart failure model.2 The authors performed a temporary balloon occlusion of the proximal left anterior descending artery to create myocardial infarction. One month later, 31 survived pigs were randomized to receive via antegrade coronary infusion either saline or adeno-associated vector type 1 (AAV1) loaded with SUMO-1 (low and high dose), SERCA2a , or both. They showed that both SUMO-1 and SERCA2a levels were increased in the pigs that received AAV1. SUMO-1 with or without AAV1. SERCA2a 2 months later. However, the changes in left ventricular ejection fraction (EF) were not statistically significant in all treated groups. Statistically significant changes were demonstrated in the maximal rate of pressure rise [d P /d t (max)] in the groups that received high-dose SUMO-1 , SERCA2a , or both. Furthermore, the treated groups have less left …

Clinical Utility of Enhanced Relative Activity Recovery on Systolic Myocardial Perfusion SPECT: Lessons from PET

SPECT and PET myocardial perfusion images show greater myocardial intensity and homogeneity in systole than diastole because of greater systolic myocardial thickness, less partial volume loss, and enhanced activity recovery. Consequently, conventional myocardial perfusion images obtained from whole cardiac cycles have lower myocardial intensity and greater heterogeneity than systolic images. Considering relative activity distribution on SPECT systolic images may add clinical utility to whole-cycle images and wall motion. Methods: Patients undergoing coronary angiogram within 4 mo after SPECT myocardial perfusion imaging were reviewed. Images were interpreted by 2 masked interpreters using a 17-segment, 5-point scale to determine summed rest scores (SSS), summed stress scores, and summed difference scores on conventional and systolic images in 603 patients (55.6% no coronary artery disease [no-CAD] and 44.4% CAD). Studies were considered normal when the SSS was less than 4 and summed difference score was less than 2. Results: In the no-CAD group, systolic SSS was lower than SSS from conventional images (2 ± 2.3 vs. 3 ± 2.6, P < 0.001). In contrast, SSS derived from systolic and conventional images were not different in the obstructive CAD group (9.1 ± 7.6 vs. 9.2 ± 7.4, P = 0.559). When systolic images were considered, true-negative studies increased from 27.2% to 43.3% (P < 0.001) whereas false-positive studies decreased from 28.4% to 12.3% (P < 0.001). True-positive (38% vs. 37.2%, P = 0.505) and false-negative studies (6.5% vs. 7%, P = 0.450) were not significantly changed. Diagnostic accuracy increased from 65.2% to 80.8% (P < 0.001). Conclusion: For gated SPECT myocardial perfusion imaging, when relative activity distribution on systolic images was considered, false-positive studies were reduced and diagnostic accuracy was improved.

Risk Prediction Model for Permanent Pacemaker Implantation after Transcatheter Aortic Valve Replacement

ABSTRACT Background: Atrioventricular conduction disturbance requiring permanent pacemaker (PPM) implantation is the most common complication after transcatheter aortic valve replacement (TAVR). Improved risk stratification for potential need for post-procedure PPM implant prior to the TAVR procedure is warranted. The aim of this study was to develop and validate a risk-prediction model for PPM implantation after TAVR. Methods: This PPM risk assessment model was developed using the 2012&2013 National Inpatient Sample (NIS). A logistic regression model was built to identify the predictors of PPM placement. The performance of the model was validated using the NIS 2014 dataset. Results: Of 18,400 patients in the development cohort, 1,825 (9.9%) patients required PPM implantation after TAVR. After multivariate analysis, final predictive covariates of PPM implantation included left or right bundle branch block, bradycardia, 2nd-degree AV block and transfemoral approach. The estimated regression coefficients associated with these predictors were used to develop a scoring system. The proposed scoring system showed good discrimination in both development and validation cohorts, with c-statistics of 0.754 (95% CI: 0.726–0.782) and 0.746 (95% CI: 0.721–0.772) respectively. Calibration analysis indicated a good agreement between the observed rate of PPM and predicted risks of PPM by the risk score. Conclusions: This PPM risk prediction model derived using the NIS database is a simple tool that can estimate individual risk of PPM prior to TAVR procedure. The model displayed good discrimination and calibration indices. This risk score can provide valuable information for patients’ counseling and also help identify high-risk patients who need close monitoring immediately after the TAVR procedure.

CARDIAC CATHETERIZATION IN CANCER PATIENTS WITH THROMBOCYTOPENIA: 4-YEAR EXPERIENCE FROM A HIGH VOLUME CANCER CENTER CARDIAC CATHETERIZATION LABORATORY

Thrombocytopenia is common in certain types of cancer. Research data and guidelines about PCI in this subgroup of patients is scarce as cancer patients have been excluded from all major PCI clinical trials. Between 11/2009 and 11/2013 a total of 1,517 consecutive cancer patients underwent cardiac

Cancer Therapy-Induced Cardiomyopathy

Modern advances in cancer treatment have resulted in a steady improvement in life expectancy in cancer patients. However, cardiovascular toxicity is one of the most devastating complications threatening to offset the substantive reductions in cancer-related morbidity and mortality that has been achieved with novel chemotherapeutic agents. Cardiologists and oncologists must collaborate closely to provide effective cancer therapy to kill cancer cells while minimizing toxicity to the cardiovascular system. Structural, functional, or biochemical indicators of cardiac injury are emerging as potential markers for early detection of cardiotoxicity. Imaging modalities such as tissue Doppler imaging, strain imaging, and cardiac magnetic resonance imaging have shown promise in earlier detection of cardiotoxicity. Biomarkers such as troponin I may also play an adjunctive role in earlier recognition of cardiotoxicity and identifying high-risk patients. There have been significant advances in the understanding of the mechanisms of cancer therapy-induced cardiotoxicity. These new pathways have been instrumental in the testing of preventive therapies. Several agents have been investigated in their ability to protect normal cardiac tissue during cancer therapy. These include dexrazoxane, angiotensin-converting enzyme inhibitors, and beta-blockers. However, further studies are warranted to clarify the efficacy, safety, and cancer treatment-related effects of these agents. Once clinical signs or symptoms of cardiac dysfunction develop, the patients should be promptly treated with standard heart failure therapy, and offending agents should be stopped. In some patients, cancer therapy may be resumed following the restoration of cardiac function. Close collaboration between the cardiologists and oncologists will herald in a new era where cancer patients will have a healthy heart to enjoy life after cancer therapy.

PREVALENCE AND RISK FACTORS OF LEFT VENTRICULAR THROMBUS IN NONISCHEMIC CARDIOMYOPATHY PATIENTS WITH SEVERE LEFT VENTRICULAR SYSTOLIC DYSFUNCTION

Previous studies have not evaluated the prevalence and the presence of specific risk factors for the development of left ventricular thrombus (LVT) among chemotherapy related cardiomyopathy (CRC) patients who develop severe left ventricular (LV) systolic dysfunction. We used echocardiographic and