Enrique Gongora

Heart failure in chemotherapy-related cardiomyopathy: Can exercise make a difference?

Medical therapies in oncology have resulted in better survival resulting in a large population who are at risk of early and late cardiac complications of chemotherapy. Cardiotoxicity related to chemotherapy can manifest decades after treatment with a threefold higher mortality rate as compared to idiopathic dilated cardiomyopathy. The leading cause of death in cancer survivors seems to be cardiac. Early detection and intervention could prevent progression of heart failure to end stage disease requiring advanced therapies such as implantation of ventricular assist devices or cardiac transplantation. This review focuses on the role of exercise in cardioprotection in this population. The current practice of depending on ejection fraction for diagnosis of heart failure is suboptimal to detect subclinical disease. It is also important to diagnose and treat early diastolic dysfunction as this tends to lead to heart failure with preserved ejection fraction. Hence we suggest an algorithm here that is based on using strain rate and tissue Doppler imaging modalities to detect subclinical systolic and diastolic dysfunction. Further research is warranted in terms of defining exercise prescriptions in this population. Human studies with multicenter participation in randomized controlled trials should be done to elucidate the intricacies of aerobic exercise intervention in cardiotoxicity dependent heart failure. It is also necessary to assess the utility of exercise interventions in the different chemotherapeutic regimens as they impact the outcomes.

MicroRNAs as therapeutic targets in cardiomyopathies: myth or reality?

Abstract The identification of biomarkers for cardiomyopathy presents a distinct challenge as the etiologies are widely varied. The discovery of small non-coding miRNAs with gene regulatory function has opened new avenues of investigation in basic and clinical sciences. The search for regulatory nucleotide sequences that have specific gene targets have put miRNAs at the forefront of development of therapeutics, and may serve as valuable diagnostic and/or therapeutic targets. MiRNAs appear to influence both positive and negative remodeling. As cardiac remodeling is a complex process, global molecular networks and miRNA profiles may be required to fulfill the roles of macroregulators. The type of cardiomyopathy leading to heart failure in the long run appears to have a distinct molecular pattern underlying the pathophysiology. This review discusses in brief the existing literature on the molecular signatures in dilated, ischemic, hypertrophic, stress, and peripartum cardiomyopathies that may be used to target therapies for specific etiologies once diagnosed, therefore exploring the utility of specific miRNAs in tailoring therapy for heart failure based on etiology.

Temporary left ventricular assist device through an axillary access is a promising approach to improve outcomes in refractory cardiogenic shock patients.

Cardiogenic shock (CS) causes significant morbidity and mortality and such patients can deteriorate rapidly. Temporary left ventricular assist devices (LVADs) are a promising approach to manage these patients. The following is a case series in which patients stabilized with a temporary LVAD for CS improvement were analyzed retrospectively. Between June 2011 and January 2014, 15 patients received temporary devices through an axillary approach (mean age: 53 ± 15, 93% male). Mean survival time was 317.8 ± 359.5 days (range: 6–936 days). During support there were no major bleeding events, infectious complications at the axillary access site, upper extremity edema, or emboli. The most of the patients recovered from CS (93%) were mobilized (67%) and were extubated (73%) while on temporary device support. Median times to extubation, intensive care unit discharge, and discontinuation of inotropic medications were: 1.63, 18, and 15 days, respectively. Four patients recovered to no device support and five received a long-term LVAD, all of whom remain alive. Therefore, implantation of a temporary LVAD through an axillary approach is a promising therapy for improving outcomes in patients needing mechanical circulatory support as a bridge to recovery or a definitive LVAD.

Oxidative Stress and Cardiovascular Aging: Interaction Between NRF-2 and ADMA

Background: The concept of antioxidant therapies assumes high importance as oxidative stress is associated with cardiovascular aging via endothelial dysfunction. This review focuses on exploring the interaction between nrf-2 and ADMA in influencing the nitric oxide pathway and cardiovascular function. Objective: A systematic review of literature from 1990 to 2016 was conducted using Pubmed and Google Scholar. The literature suggests a strong influence of nrf-2 activation on up regulation of DDAH I which degrades ADMA, the endogenous inhibitor of nitric oxide synthase. The resulting decrease of ADMA would in turn enhance nitric oxide (NO) production. This would support endothelial function by adequate NO production and homeostasis of endothelial function. Conclusion: As NO production has many positive pleiotropic effects in the cardiovascular system, such an interaction could be utilized for designing molecular therapeutics. The targets for therapy need not be limited to activation of nrf-2. Modulation of molecules downstream such as DDAH I can be used to regulate ADMA levels. Most current literature is supported by animal studies. The concept of antioxidant therapies needs to be tested in well-defined randomized control trials. The biochemical basis of nrf-2 activation needs to be substantiated in human studies.

Pump Outflow Graft Puncture in a Patient With a HeartMate II Ventricular Assist Device

A 73-year-old patient supported by a HeartMate II ventricular assist device (VAD) (Thoratec Corp, Pleasanton, CA) experienced erosion of the outflow graft caused by the disconnection of the bend relief. He underwent successful surgical repair.

Role of cardiovascular imaging in selection of donor hearts

AIM To perform a systematic review of literature on use of cardiovascular imaging in assessment of donor hearts. METHODS A systematic search of current literature from January 1965 to August 2015 was performed using PubMed and Google Scholar to investigate the different imaging modalities used to assess donor hearts. RESULTS Recent literature still estimates only a 32% utilization of available donor hearts in the United States. Most common imaging modality used is transthoracic echocardiography. Use of advanced imaging modalities such as 3D echocardiography, cardiac computer tomography and cardiac magnetic resonance to evaluate donor hearts is not reported in literature. This review attempts to highlight the relevant imaging modalities that can be used to assess cardiac function in a time-efficient manner. The algorithm suggested in this review would hopefully pave the way to standardized protocols that can be adopted by organ procuring organizations to increase the donor pool. CONCLUSION Use of advanced imaging techniques for a thorough assessment of organs will likely increase the donor pool.

Correlations of GDF-15 with sST2, MMPs, and worsening functional capacity in idiopathic dilated cardiomyopathy: Can we gain new insights into the pathophysiology?

Growth and differentiation factor-15 (GDF-15) has been implicated in fibrosis, inflammation, and ventricular remodeling. The role of GDF-15 in the regulation of cardiac remodeling in idiopathic dilated cardiomyopathy (DCM) remains poorly defined. This study attempts to analyze the molecular interactions between GDF-15 and markers of fibrosis as well as its positive correlations with worsening functional capacity. The study population consisted of 24 DCM patients and 8 control subjects. All DCM patients had normal coronary angiographic studies. Plasma levels of GDF-15, matrix metalloproteinase-2 (MMP2), MMP3, MMP9, tissue inhibitor of MMP 1 (TIMP1), and soluble suppression of tumorigenicity-2 protein (sST2) were determined by enzyme-linked immunosorbent assays. Brain Natriuretic Peptide (BNP) was measured as per core laboratory protocol assay at Scott and White Memorial Hospital core laboratory. Correlation analysis was performed between GDF-15 and each of the MMPs—MMP2, MMP3, MMP9, and TIMP as well as New York Heart Association (NYHA) class and echocardiographic parameters (left ventricular ejection fraction (LVEF) and left ventricular internal dimension in diastole (LVIDd)). LVEF and LVIDd were obtained by two-dimensional echocardiography. The protocol was approved by Scott and White Memorial Hospital Institutional Review Board (S&W IRB). Correlation analysis of control versus all DCM patients showed a strong correlation of GDF-15 with TIMP1 (r = 0.83, p < 0.0001) and weaker correlation with MMP3 (r = 0.41, p = 0.011) and MMP2 (r = 0.47, p = 0.003). MMP9 showed poor correlation with GDF-15 (r = 0.3036, p = 0.046). GDF-15 correlated negatively with MMP2/TIMP1 ratio (r = −0.47, p = 0.006). sST2 correlated strongly with GDF-15 (r = 0.7, p < 0.0001). GDF-15 correlated negatively with LVEF (r = −0.49, p = 0.004) and positively with LVIDd (r = 0.58, p = 0.0006). GDF-15 showed significant positive correlation with NYHA functional class (r = 0.71, p < 0.00001) and BNP (r = 0.86, p < 0.00001). Significant associations of GDF-15 with MMPs, sST2, LVIDd, LVEF, and NYHA class reported here for the first time in nonischemic dilated hearts may open up new avenues of investigations to better understand molecular mechanisms controlling cardiac remodeling. This study is limited by its small size and needs validation in larger populations.

Left ventricular assist devices in end-stage heart failure with “fixed” pulmonary hypertension-a test of reversibility?

Pulmonary hypertension (PH) secondary to left heart disease is one of the risk factors for morbidity and mortality after orthotopic heart transplantation. In cardiac allograft recipients PH can lead to acute right ventricular failure resulting in high mortality rates. When longstanding PH becomes refractory to medical treatment, it is considered “fixed”; at this stage vasodilator challenges do not produce any decrease in pulmonary artery pressures or the calculated pulmonary vascular resistance. Mixed PH is also called PH out-of-proportion to left-sided filling pressures and consists of increased left-sided filling pressures in addition to elevated pulmonary vascular resistance. Mixed PH that is responsive to vasodilator challenge is called reversible / reactive or vasoreactive PH, but mixed PH that is not reversible is called irreversible or fixed or refractory or persistent PH. Fixed PH (>2.5 Wood units) is an absolute contraindication to cardiac transplantation due to its detrimental effects on the right ventricular function. When pharmacological agents fail to decrease left ventricular filling pressures chronically, mechanical unloading becomes necessary to reverse the PH due to left heart disease. Unloading the left ventricle with a left ventricular assist device (LVAD) progressively decreases pulmonary vascular resistance to normal values in patients making them eligible for heart transplantation. Contraindications for LVAD implant include active infection/malignancy or end stage renal disease at the time of implant. In a small study of ten patients with severe pulmonary hypertension refractory to medical treatment, continuous flow mechanical support was provided as a bridge to transplant. Pulmonary artery pressures, transpulmonary gradients, and pulmonary vascular resistance were all significantly decreased after 1-6 months of LVAD support, suggesting that medically unresponsive PH can be reversed by mechanical unloading of the LV. This approach has increased survival in patients whose fixed PH was reversed prior to transplantation. 7 LVAD therapy is also applicable to patients with RV failure secondary to LV failure. Therefore, the use of LVADs as a bridge to cardiac transplantation has gained momentum and importance in this patient population. Table 1 shows the outcomes in small studies using LVADs to reverse PH secondary to left heart disease. Factors that actively determine reversibility of PH due to left heart disease are not clear in the existing literature. Hence, no selection criteria can be currently used in these patients except for the fact that they have PH refractory to medical therapy. Another interesting aspect of LVAD support in reversing secondary PH is the role of continuous flow (CF) pumps versus pulsatile pumps. In a small single center study of 27 LVAD patients (15 with CF pumps [Heart Ware Inc., Framingham, MA] and 12 with pulsatile pumps [Berlin Heart EXCOR, Berlin, Germany]), the patients with CF pumps had greater reductions in pulmonary artery systolic pressures. No significant differences were noted in right ventricular systolic motion, tricuspid annular plane systolic excursion, and right ventricular ejection fraction. In another single center prospective study, 29 patients with centrifugal pumps had significant improvement in their transpulmonary gradients, pulmonary artery systolic pressures, mean pulmonary artery pressures, and pulmonary vascular resistance. These differences developed within one month post implantation. Patients bridged with centrifugal CF pumps had post-transplant survival comparable to those who were transplanted directly. The improved reduction in pulmonary artery systolic pressures in patients managed with CF pumps has been attributed to the fact that CF pumps unload the Corresponding author: Nandini Nair Contact Information: nandini.nair@ttuhsc.edu DOI: 10.12746/swrccc2016.0416.213