Carlos Manrique

Bio: Carlos Manrique is an academic researcher from Montefiore Medical Center. The author has contributed to research in topics: Cancer & Heart failure. The author has an hindex of 5, co-authored 12 publications receiving 277 citations. Previous affiliations of Carlos Manrique include Albert Einstein College of Medicine & University of Texas Health Science Center at Houston.

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC/D): A Systematic Literature Review

Abstract: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetic form of cardiomyopathy (CM) usually transmitted with an autosomal dominant pattern. It primary affects the right ventricle (RV), but may involve the left ventricle (LV) and culminate in biventricular heart failure (HF), life threatening ventricular arrhythmias and sudden cardiac death (SCD). It accounts for 11%–22% of cases of SCD in the young athlete population. Pathologically is characterized by myocardial atrophy, fibrofatty replacement and chamber dilation. Diagnosis is often difficult due to the nonspecific nature of the disease and the broad spectrum of phenotypic variations. Therefore consensus diagnostic criteria have been developed and combined electrocardiography, echocardiography, cardiac magnetic resonance imaging (CMRI) and myocardial biopsy. Early detection, family screening and risk stratification are the cornerstones in the diagnostic evaluation. Implantable cardioverter-defibrillator (ICD) implantation, ablative procedures and heart transplantation are currently the main therapeutic options.

Cardiac Safety of Paclitaxel Plus Trastuzumab and Pertuzumab in Patients With HER2-Positive Metastatic Breast Cancer

Abstract: Introduction Myocardial strain imaging and blood biomarkers have been proposed as adjuncts to left ventricular ejection fraction (LVEF) monitoring for the early detection of cardiotoxicity during cancer therapy. We report the results of a preplanned cardiac safety analysis of global longitudinal strain (GLS), and troponin-I (TnI) and brain natriuretic peptide (BNP) levels in the phase II study of paclitaxel, trastuzumab, and pertuzumab (THP) for metastatic HER2-positive breast cancer. Patients and methods Patients with 0-1 lines of prior therapy were treated with weekly paclitaxel (80 mg/m(2)) plus trastuzumab (8 mg/kg loading dose followed by 6 mg/kg) and pertuzumab (840 mg loading dose followed by 420 mg) every 3 weeks. Exploratory endpoints were GLS measured with speckle-tracking echocardiography every 3 months and TnI and BNP levels measured every 6 weeks (immediately pre- and postchemotherapy infusion) at 6 time points. Results Sixty-seven of 69 enrolled patients were treated with THP: 19 (28%) had hypertension, 8 (12%) had diabetes, 11 (16%) had hyperlipidemia, and 26 (38%) had smoking history. After a median follow-up of 21 months (range: 3-38 months), no patients developed symptomatic heart failure. Two patients (3.0%) experienced asymptomatic LVEF decline (grade 2). The mean GLS (±SD) was 19% ± 2% (baseline), 19% ± 2% (month 6), and 19% ± 3% (month 12). Detectable TnI (>0.06 ng/mL) and elevated BNP (>100 pg/mL) levels were observed in 3 (4.3%) and 2 (3.0%) patients, respectively, but were not associated with LVEF decline. Conclusion The absence of any significant changes in GLS and cardiac biomarkers (TnI and BNP) further support the cardiac safety of THP in patients with metastatic HER2-positive breast cancer. Implications for practice Dual anti-HER2 therapy with trastuzumab and pertuzumab in combination with taxane-based chemotherapy improves overall survival in patients with metastatic HER2-positive breast cancer. There is a critical need to investigate the potential cardiotoxicity of dual anti-HER2 blockade, given the importance of HER2 signaling in cardiac homeostasis and stress response. Global longitudinal strain and cardiac biomarkers have been proposed as adjuncts to left ventricular ejection fraction for the early detection of cardiotoxicity. In this phase II study of combination trastuzumab and pertuzumab with paclitaxel, no clinically significant change was observed in global longitudinal strain or cardiac biomarkers. These results further support the cardiac safety of dual anti-HER2 blockade previously reported in the CLEOPATRA study. The findings in the current study also call into question the role of intensive cardiac monitoring among patients treated with anti-HER2 therapy in the absence of anthracyclines. Less frequent cardiac assessments could lead to a reduction in unnecessary treatment interruption and is an important consideration given the rise in medical expenditures, but this requires further investigation.

Diagnostic Strategies for Early Recognition of Cancer Therapeutics–Related Cardiac Dysfunction

Abstract: Cardiovascular toxicity in the form of cardiac dysfunction continues to be an obstacle for patients with cancer. Survival and quality of life of cancer survivors are frequently affected by increased incidence of cardiovascular disease. The involvement of the cardiovascular system by primary or secondary malignancies, as well as its dysfunction secondary to the administration of antineoplastics, has led to the development of a new discipline called Cardio-Oncology, an exciting cardiology subspecialty with more questions than answers and as a result an enormous opportunity for research in the field. Multidisciplinary efforts have been focused on the prevention, diagnosis, and treatment of cancer therapeutics–related cardiovascular dysfunction (CTRCD). This review article will focus on the early diagnosis of left ventricular dysfunction associated with chemotherapy. Currently, the identification of cardiac toxicity associated with cancer treatment is the cornerstone for critical decisions regarding anticancer therapy and cardioprotective strategies. Its early detection, especially in subclinical phases, allows immediate intervention to prevent further impairment of the myocardium and other cardiovascular structures. The most significant published studies were selected for this revision, providing an updated document for the health professionals involved in the care of patients with cancer. We examined the current evidence and recommendations for biochemical and noninvasive diagnostic techniques, including their specific role for identification of CTRCD. Traditional and advanced imaging modalities, used alone or in combination with cardiovascular biomarkers, are essential for the recognition of cardiotoxicity during cancer therapy. Evolving basic and clinical research are focused on the development of more sensitive and specific diagnostic tools and for the recognition of cardiac toxicity.

Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia： Proposed Modification of the Task Force Criteria

Abstract: The original 1994 International Task Force criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC / D) were based on structural,histological,ECG,arrhythmic,and familial features of the disease (Table 1)Abnormalities were subdivided into major and minor categories according to the specificity of their association with ARVC / DRight precordial T-wave inversion,though well recognized in ARVC / D,was considered a minor criterion because of its presence in other conditions,including anterior ischemia and right ventricular (RV) hypertrophyArrhythmias of RV origin,another cardinal feature of ARVC / D,was designated a minor criterion because of its occurrence in other diseases,particularly idiopathic RV outflow tract tachycardia

General cardiology: abstractValvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of hodgkin lymphoma treated with radiation therapy

Abstract: CONTEXT The majority of patients with Hodgkin lymphoma are young and highly curable. This necessitates concern for prevention, diagnosis, and optimal management of potential treatment-related complications. OBJECTIVE To identify and quantify the incidence of and factors contributing to long-term cardiac and vascular complications after radiation therapy for Hodgkin lymphoma. DESIGN AND SETTING Retrospective study comparing patients treated from 1962 to 1998 at a university-based referral center with a matched general population. PATIENTS Four hundred fifteen consecutive patients who fulfilled the inclusion criteria of a minimum 2-year follow-up (median, 11.2 years) and whose radiation fields included the heart or carotid or subclavian arteries. MAIN OUTCOME MEASURES Multivariable analyses of potential risk factors and observed-to-expected ratios for cardiac valve surgery, coronary artery bypass graft surgery, percutaneous coronary intervention, or both based on Surveillance, Epidemiology, and End Results (SEER) and National Hospital Discharge Survey (NHDS) data. RESULTS Forty-two patients (10.4%) developed coronary artery disease at a median of 9 years after treatment, 30 patients (7.4%) developed carotid and/or subclavian artery disease at a median of 17 years after treatment, and 25 patients (6.2%) developed clinically significant valvular dysfunction at a median of 22 years. The most common valve lesion was aortic stenosis, which occurred in 14 valves. The observed-to-expected ratio for valve surgery was 8.42 (95% confidence interval [CI], 3.20-13.65) and the observed-to-expected ratio for coronary artery bypass graft surgery or percutaneous coronary intervention was 1.63 (95% CI, 0.98-2.28). At least 1 cardiac risk factor was present in all patients who developed coronary artery disease. The only treatment-related factor associated with the development of coronary artery disease was utilization of a radiation technique that resulted in a higher total dose to a portion of the heart (relative risk, 7.8; 95% CI, 1.1-53.2; P =.04). No specific treatment-related factor was associated with carotid or subclavian artery disease or valvular dysfunction. Freedom from any cardiovascular morbidity was 88% at 15 years and 84% at 20 years. CONCLUSIONS Among patients treated with radiation therapy for Hodgkin lymphoma, there are statistically higher than expected rates of valve surgery and coronary revascularization procedures over the next 10 to 20 years. Coronary vascular disease is associated with higher radiation doses and traditional coronary heart disease risk factors. Noncoronary vascular disease and clinically important valvular dysfunction are less well understood complications at 15 to 20 years after radiation, requiring surveillance and further study.

A water-soluble nucleolin aptamer-paclitaxel conjugate for tumor-specific targeting in ovarian cancer

Abstract: Paclitaxel (PTX) is among the most commonly used first-line drugs for cancer chemotherapy. However, its poor water solubility and indiscriminate distribution in normal tissues remain clinical challenges. Here we design and synthesize a highly water-soluble nucleolin aptamer-paclitaxel conjugate (NucA-PTX) that selectively delivers PTX to the tumor site. By connecting a tumor-targeting nucleolin aptamer (NucA) to the active hydroxyl group at 2' position of PTX via a cathepsin B sensitive dipeptide bond, NucA-PTX remains stable and inactive in the circulation. NucA facilitates the uptake of the conjugated PTX specifically in tumor cells. Once inside cells, the dipeptide bond linker of NucA-PTX is cleaved by cathepsin B and then the conjugated PTX is released for action. The NucA modification assists the selective accumulation of the conjugated PTX in ovarian tumor tissue rather than normal tissues, and subsequently resulting in notably improved antitumor activity and reduced toxicity.

European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation.

Abstract: The cohort of long-term survivors of heart transplant is expanding, and the assessment of these patients requires specific knowledge of the surgical techniques employed to implant the donor heart, the physiology of the transplanted heart, complications of invasive tests routinely performed to detect graft rejection (GR), and the specific pathologies that may affect the transplanted heart. A joint EACVI/Brazilian cardiovascular imaging writing group committee has prepared these recommendations to provide a practical guide to echocardiographers involved in the follow-up of heart transplant patients and a framework for standardized and efficient use of cardiovascular imaging after heart transplant. Since the transplanted heart is smaller than the recipient's dilated heart, the former is usually located more medially in the mediastinum and tends to be rotated clockwise. Therefore, standard views with conventional two-dimensional (2D) echocardiography are often difficult to obtain generating a large variability from patient to patient. Therefore, in echocardiography laboratories equipped with three-dimensional echocardiography (3DE) scanners and specific expertise with the technique, 3DE may be a suitable alternative to conventional 2D echocardiography to assess the size and the function of cardiac chambers. 3DE measurement of left (LV) and right ventricular (RV) size and function are more accurate and reproducible than conventional 2D calculations. However, clinicians should be aware that cardiac chamber volumes obtained with 3DE cannot be compared with those obtained with 2D echocardiography. To assess cardiac chamber morphology and function during follow-up studies, it is recommended to obtain a comprehensive echocardiographic study at 6 months from the cardiac transplantation as a baseline and make a careful quantitation of cardiac chamber size, RV systolic function, both systolic and diastolic parameters of LV function, and pulmonary artery pressure. Subsequent echocardiographic studies should be interpreted in comparison with the data obtained from the 6-month study. An echocardiographic study, which shows no change from the baseline study, has a high negative predictive value for GR. There is no single systolic or diastolic parameter that can be reliably used to diagnose GR. However, in case several parameters are abnormal, the likelihood of GR increases. When an abnormality is detected, careful revision of images of the present and baseline study (side-by-side) is highly recommended. Global longitudinal strain (GLS) is a suitable parameter to diagnose subclinical allograft dysfunction, regardless of aetiology, by comparing the changes occurring during serial evaluations. Evaluation of GLS could be used in association with endomyocardial biopsy (EMB) to characterize and monitor an acute GR or global dysfunction episode. RV size and function at baseline should be assessed using several parameters, which do not exclusively evaluate longitudinal function. At follow-up echocardiogram, all these parameters should be compared with the baseline values. 3DE may provide a more accurate and comprehensive assessment of RV size and function. Moreover, due to the unpredictable shape of the atria in transplanted patients, atrial volume should be measured using the discs' summation algorithm (biplane algorithm for the left atrium) or 3DE. Tricuspid regurgitation should be looked for and properly assessed in all echocardiographic studies. In case of significant changes in severity of tricuspid regurgitation during follow-up, a 2D/3D and colour Doppler assessment of its severity and mechanisms should be performed. Aortic and mitral valves should be evaluated according to current recommendations. Pericardial effusion should be serially evaluated regarding extent, location, and haemodynamic impact. In case of newly detected pericardial effusion, GR should be considered taking into account the overall echocardiographic assessment and patient evaluation. Dobutamine stress echocardiography might be a suitable alternative to routine coronary angiography to assess cardiac allograft vasculopathy (CAV) at centres with adequate experience with the methodology. Coronary flow reserve and/or contrast infusion to assess myocardial perfusion might be combined with stress echocardiography to improve the accuracy of the test. In addition to its role in monitoring cardiac chamber function and in diagnosis the occurrence of GR and/or CAV, in experienced centres, echocardiography might be an alternative to fluoroscopy to guide EMB, particularly in children and young women, since echocardiography avoids repeated X-ray exposure, permits visualization of soft tissues and safer performance of biopsies of different RV regions. Finally, in addition to the indications about when and how to use echocardiography, the document also addresses the role of the other cardiovascular imaging modalities during follow-up of heart transplant patients. In patients with inadequate acoustic window and contraindication to contrast agents, pharmacological SPECT is an alternative imaging modality to detect CAV in heart transplant patients. However, in centres with adequate expertise, intravascular ultrasound (IVUS) in conjunction with coronary angiography with a baseline study at 4-6 weeks and at 1 year after heart transplant should be performed to exclude donor coronary artery disease, to detect rapidly progressive CAV, and to provide prognostic information. Despite the fact that coronary angiography is the current gold-standard method for the detection of CAV, the use of IVUS should also be considered when there is a discrepancy between non-invasive imaging tests and coronary angiography concerning the presence of CAV. In experienced centres, computerized tomography coronary angiography is a good alternative to coronary angiography to detect CAV. In patients with a persistently high heart rate, scanners that provide high temporal resolution, such as dual-source systems, provide better image quality. Finally, in patients with insufficient acoustic window, cardiac magnetic resonance is an alternative to echocardiography to assess cardiac chamber volumes and function and to exclude acute GR and CAV in a surveillance protocol.