Sadeer G. Al-Kindi

Prevalence of Preexisting Cardiovascular Disease in Patients With Different Types of Cancer: The Unmet Need for Onco-Cardiology

Cancer and cardiovascular diseases (CVDs) share many of the same risk factors. Using a cloud-based health care database, we identified patients with malignancies that often require cardiotoxic treatments (leukemia/lymphoma and lung, breast, colon, renal, and head and neck cancers). We report the prevalence of CVDs (coronary artery disease, carotid artery disease, peripheral vascular disease, cerebrovascular disease, and heart failure) in those populations. Overall, CVD prevalences were 33% for hematologic, 43% for lung, 17% for breast, 26% for colon, 35% for renal, and 26% for head and neck cancers. Generally, patients with lung and hematologic malignancies had the highest prevalence of all types of CVDs. Of those with CVD, only half were referred to cardiologists and received guideline-directed medical therapy. The prevalence of CVDs is unexpectedly high and suboptimally managed in patients with cancer. There seems to be an opportunity for onco-cardiologists to fulfill this unmet need and help improve outcomes in patients with cancer and coexisting heart disease.

Model for end-stage liver disease excluding international normalized ratio (MELD-XI) score predicts heart transplant outcomes: Evidence from the registry of the United Network for Organ Sharing

BACKGROUND Hepato-renal function is a valuable predictor of success after left ventricular assist device therapy and heart transplantation. Hence, we analyzed the importance of the Model for End-stage Liver Disease excluding international normalized ratio (MELD-XI) score to outcomes after heart transplant. METHODS Adults undergoing heart transplant from the United Network for Organ Sharing (UNOS) database were identified (1994 to 2014). Individual MELD-XI scores were calculated; patients were stratified by MELD-XI quartiles (Q1 to Q4). Multivariate logistic regression and the Cox proportional hazard model were implemented to determine any association between MELD-XI scores, survival and other outcomes. RESULTS From 39,711 patients undergoing OHT during the study period, MELD-XI score [median 10.7 (interquartile range 7.0 to 14.4)] was calculated for 36,005 patients (76% male and 75% white, 34% Status 1A). Higher MELD-XI scores had higher rates of pre-transplant extracorporeal membrane oxygenation, intra-aortic balloon pump, inotrope use and mechanical ventilation (p < 0.001 for all). Adjusted long-term mortality (median follow-up 8.1 years) was associated with MELD-XI score (hazard ratio [HR] 1.021 [1.016 to 1.026], p < 0.001). The highest MELD-XI quartile was associated with an HR 1.364 [1.255 to 1.482] risk of mortality compared with Q1. MELD-XI score was also associated with increased post-transplant infections (adjusted HR Q4 vs Q1: 1.364 [1.153 to 1.614], p < 0.001), stroke (adjusted HR Q4 vs Q1: 1.410 [1.074 to 1.852], p = 0.013), dialysis (adjusted HR Q4 vs Q1: 3.982 [3.386 to 4.683], p < 0.001), rejection (adjusted HR Q4 vs Q1: 1.519 [1.286 to 1.795], p = 0.003) and prolonged hospitalization (adjusted HR Q4 vs Q1: 1.635 [1.429 to 1.871], p < 0.001). CONCLUSION Hepato-renal dysfunction, measured with MELD-XI score, predicts morbidity and mortality in patients undergoing orthotopic heart transplantation. Etiology of hepato-renal dysfunction should be sought and treated before heart transplantation.

Characteristics and Survival of Malignant Cardiac Tumors A 40-Year Analysis of >500 Patients

Background— The aim of this study was to investigate the incidence, histopathology, demographics, and survival associated with primary malignant cardiac tumors (PMCTs). Methods and Results— We queried the Surveillance, Epidemiology and End Results (SEER) 18 registry from the National Cancer Institute for all PMCTs diagnosed from 1973 to 2011. We describe PMCT histopathology and incidence, comparing characteristics and survival of these patients with those of patients with extracardiac malignancies of similar histopathology. From a total of 7 384 580 cases of cancer registered in SEER, we identified 551 PMCTs (0.008%). The incidence of PMCT diagnosis is 34 cases per 100 million persons and has increased over time (25.1 in 1973–1989, 30.2 in 1990–1999, and 46.6 in 2000–2011). Most patients are female (54.1%) and white (78.6%) with median age at diagnosis of 50 years. The most common PMCTs are sarcomas (n=357, 64.8%), followed by lymphomas (n=150, 27%) and mesotheliomas (n=44, 8%). Most patients are diagnosed with tissue sample (96.8%). Although use of chemotherapy is not documented in SEER, 19% of patients received radiation and 44% had surgery. After a median follow-up of 80 months, 413 patients had died. The 1-, 3-, and 5-year survival rates were 46%, 22%, and 17% and have improved over the eras, with 1-, 3-, and 5-year survival rates of 32%, 17%, and 14% for 1973 to 1989 and 50%, 24%, and 19% for 2000 to 2011 ( P =0.009). Cardiac sarcomas and mesotheliomas are the most lethal PMCTs, with 1-, 3-, 5-year survival rates of 47%, 16%, and 11% and of 51%, 26%, and 23% compared with 59%, 41%, and 34% for lymphomas, respectively (log rank test P <0.001). Patients with cardiac lymphomas and sarcomas are younger and have worse survival than patients with extracardiac disease of similar histopathology ( P <0.001). Conclusions— PMCTs are extremely rare and continue to be associated with poor prognosis. Over the past 5 decades, the incidence and survival of patients diagnosed with PMCT appear to have increased. Compared with those with extracardiac cancers of similar histopathology, patients with PMCTs are often younger and have worse survival. # CLINICAL PERSPECTIVE {#article-title-40}Background— The aim of this study was to investigate the incidence, histopathology, demographics, and survival associated with primary malignant cardiac tumors (PMCTs). Methods and Results— We queried the Surveillance, Epidemiology and End Results (SEER) 18 registry from the National Cancer Institute for all PMCTs diagnosed from 1973 to 2011. We describe PMCT histopathology and incidence, comparing characteristics and survival of these patients with those of patients with extracardiac malignancies of similar histopathology. From a total of 7 384 580 cases of cancer registered in SEER, we identified 551 PMCTs (0.008%). The incidence of PMCT diagnosis is 34 cases per 100 million persons and has increased over time (25.1 in 1973–1989, 30.2 in 1990–1999, and 46.6 in 2000–2011). Most patients are female (54.1%) and white (78.6%) with median age at diagnosis of 50 years. The most common PMCTs are sarcomas (n=357, 64.8%), followed by lymphomas (n=150, 27%) and mesotheliomas (n=44, 8%). Most patients are diagnosed with tissue sample (96.8%). Although use of chemotherapy is not documented in SEER, 19% of patients received radiation and 44% had surgery. After a median follow-up of 80 months, 413 patients had died. The 1-, 3-, and 5-year survival rates were 46%, 22%, and 17% and have improved over the eras, with 1-, 3-, and 5-year survival rates of 32%, 17%, and 14% for 1973 to 1989 and 50%, 24%, and 19% for 2000 to 2011 (P=0.009). Cardiac sarcomas and mesotheliomas are the most lethal PMCTs, with 1-, 3-, 5-year survival rates of 47%, 16%, and 11% and of 51%, 26%, and 23% compared with 59%, 41%, and 34% for lymphomas, respectively (log rank test P<0.001). Patients with cardiac lymphomas and sarcomas are younger and have worse survival than patients with extracardiac disease of similar histopathology (P<0.001). Conclusions— PMCTs are extremely rare and continue to be associated with poor prognosis. Over the past 5 decades, the incidence and survival of patients diagnosed with PMCT appear to have increased. Compared with those with extracardiac cancers of similar histopathology, patients with PMCTs are often younger and have worse survival.

Left Ventricular Restoration Devices

Left ventricular (LV) remodeling results in continuous cardiac chamber enlargement and contractile dysfunction, perpetuating the syndrome of heart failure. With current exhaustion of the neurohormonal medical paradigm, surgical and device-based therapies have been increasingly investigated as a way to restore LV chamber architecture and function. Left ventricular restoration has been attempted with surgical procedures, such as partial left ventriculectomy, surgical ventricular restoration with or without revascularization, and devices, such as the Acorn CorCap, the Paracor HeartNet, and the Myocor Myosplint. Whereas all these techniques require surgical access, with or without cardiopulmonary bypass, a newer ventricular partitioning device (VPD) called Parachute, can be delivered percutaneously through the aortic valve. Designed to achieve LV restoration from within the ventricle, this VPD partitions the LV by isolating aneurysmal from normal myocardium thereby diminishing the functioning cavity. This review aims to critically appraise the above methods, with particular attention to device-based therapies.

Advanced Heart Failure Therapies for Patients With Chemotherapy-Induced Cardiomyopathy

Continual advances in antineoplastic therapies have produced better cancer outcomes with 13.7 million cancer survivors in the United States in 20131. However, a significant number of survivors may develop cardiac disease as a result of cancer treatment, whether chemotherapy, radiation, or a combination of both.2 Although radiation can cause significant heart disease3 both alone and with chemotherapy, this review will only address cardiomyopathy induced by chemotherapy agents, especially anthracyclines, commonly used to treat pediatric and adult cancers. Whereas anthracyclines remain the most common cause of chemotherapy-induced cardiomyopathy (CCMP), recently developed targeted therapies can also cause cardiac dysfunction.4–6 Newer drugs that target survival pathways in cancer cells, such as the HER-2 (human epidermal growth factor 2) and vascular endothelial growth factor inhibitors, have been directly implicated in left ventricular (LV) systolic dysfunction7,8 through off-target effects. Because cancer and heart cells share many of the same survival pathways, it is likely that newer targeted therapies will continue to cause off-target impairment of cardiomyocyte survival and heart failure (HF).9 However, whereas LV dysfunction associated with targeted therapies seems reversible,10 anthracyclines remain the only agents that seem capable to cause end-stage HF.11 In this review, we critically appraise the data available to support the use of advanced HF therapies in this patients with CCMP and end-stage HF. Specifically, we review treatments indicated for American College of Cardiology/American Heart Association stages C-D HF, including implantable cardiac defibrillators, cardiac resynchronization therapy (CRT), mechanical circulatory support devices, and orthotopic heart transplantation (OHT). Herein defined as cardiomyopathy caused by anthracycline damage with or without exposure to other cardiotoxic agents,12 CCMP has been described in 1% to 5% of cancer survivors13,14 and arguably portends the worst survival among cardiomyopathies.15 Unlike any …

Heart Transplantation Outcomes in Radiation-Induced Restrictive Cardiomyopathy

BACKGROUND Some cancer therapies can cause advanced heart failure requiring heart transplantation. Although dilated cardiomyopathy is the most common phenotype, those who receive radiation may develop restrictive cardiomyopathy. The characteristics and transplantation outcomes patients with radiation-induced restrictive cardiomyopathy are not established. METHODS AND RESULTS We used United Network for Organ Sharing registry to identify adults who were listed for heart transplantation between 2000 and 2015 for radiation-induced restrictive cardiomyopathy (RT-RCM) and compared their characteristics and transplant outcomes to restrictive cardiomyopathies of other etiologies (RCM) and all other patients listed for heart transplantation (others). Of 45,041 adults, 87 (0.2%) of transplantations were due to RT-RCM, 1049 (2.3%) were due to RCM, and there were 44,805 others. Compared with patients with RCM and other etiologies, those with RT-RCM were younger, less likely male, more likely to be white, listed as status 2, and were also more likely to have had previous cardiac surgeries. Posttransplant, patients with RT-RCM had longer lengths of stay and higher early mortality; 1-, 3-, and 5-year cumulative survival were as follows for RT-RCM (76%, 66%, 58%), RCM (88%, 79%, 73%; P = .025 compared with RT-RCM), and other etiologies (88%, 82%, 76%; P = .012 compared with RT-RCM). CONCLUSIONS Patients with end-stage RT-RCM are predominantly younger females with previous cardiac surgeries. Posttransplantation survival in these patients appears to be lower than in those with other forms of restrictive cardiomyopathies and heart failure etiologies, mainly because of higher early postoperative mortality. Further studies are needed to confirm these findings.

Left Ventricular Assist Devices or Inotropes for Decreasing Pulmonary Vascular Resistance in Patients with Pulmonary Hypertension Listed for Heart Transplantation

BACKGROUND Fixed pulmonary hypertension is common in patients with advanced heart failure and is a contraindication for heart transplantation. Left ventricular assist devices (LVAD) and inotropes have been used to reduce pulmonary vascular resistance (PVR) and allow transplantation. However, little is known about the efficacy of this strategy. METHODS We queried the United Network for Organ Sharing registry for all adult patients (age ≥18 years) listed for primary heart transplantation (2008-2014) with PVR of >5 wood units (WU) or transpulmonary gradient >16 mmHg who were treated with LVAD or IV inotropes as status 1a, 1b, or 7. We compared waitlist mortality/delisting and absolute changes in hemodynamics between listing and transplantation. RESULTS Of 18,009 patients listed during the study period, 1016 were included in the analysis (393 LVAD, 623 inotropes), with a mean age of 52.9 ± 11.6 years, 74% male, and 38% had ischemic etiology. Mean PVR was 5.7 ± 2.4 WU and transpulmonary pressure gradient 19.3 ± 5.3 mmHg. Compared with the inotrope group, LVAD patients were more likely listed as status 1A (32.8% vs 18.1%, P < .001), had lower PVR (5.3 WU vs 5.9 WU, P = .001), and higher cardiac output (4.1 vs 3.6 L/min, P < .001). After a mean of 239 days, PVR decreased by 1.71 WU in the LVAD group vs 1.85 WU in the inotrope group (P = .52). PVR normalization (<2.5 WU) occurred at similar rates among those treated with inotropes and LVAD (30.7% vs 35.6%, P = .228). Waitlist mortality was similar between LVAD and inotropes (adjusted P = .837). Absolute PVR and transpulmonary pressure gradient reductions correlated with time on the waitlist (P < .001 for both comparisons). CONCLUSION Only about one-third of patients with fixed pulmonary hypertension achieve normalization of PVR before transplant with either LVAD or inotropes. Similar waitlist mortality was observed among patients bridged with either strategy.

Heart failure in patients with human immunodeficiency virus infection: Epidemiology and management disparities.

BACKGROUND Persons living with HIV are at a higher risk of cardiovascular disease despite effective antiretroviral therapy and dramatic reductions in AIDS-related conditions. We sought to identify the epidemiology of heart failure (HF) among persons living with HIV in the United States in an era of contemporary antiretroviral therapy. METHODS Explorys is an electronic healthcare database that aggregates medical records from 23 healthcare systems nationwide. Using systemized nomenclature of medicine-clinical terms (SNOMED-CT), we identified adult patients (age>18), who had active records over the past year (September 2014-September 2015). We described the prevalence of HF in HIV patients by demographics and treatment and compared them to HIV-uninfected controls. RESULTS Overall, there were 36,400 patients with HIV and 12,208,430 controls. The overall prevalence of HF was 7.2% in HIV and 4.4% in controls (RR 1.66 [1.60-1.72], p<0.0001). The relative risk of HF associated with HIV infection was higher among women and younger age groups. Patients receiving antiretroviral therapy had only marginally lower risk (6.4% vs. 7.7%, p<0.0001) of HF compared to those who were untreated. Compared to uninfected patients with HF, HIV patients with HF were less likely to receive antiplatelet drugs, statins, diuretics, and ACE/ARBs (p<0.0001 for all comparisons). For patients with HIV and HF, receiving care from a cardiologist was associated with higher use of antiplatelets, statins, betablockers, ACE/ARBs, and diuretics. CONCLUSIONS Persons with HIV are at higher risk for HF in this large contemporary sample that includes both men and women. Although the prevalence of heart failure is higher in older HIV patients, the relative risk associated with HIV is highest in young people and in women. HIV patients are less likely to have HF optimally treated, but cardiology referral was associated with higher treatment rates.

Cardiovascular disease research activity in the Middle East: a bibliometric analysis

Objectives: The Middle East has a high prevalence of noncommunicable chronic diseases. The objective of this article was to quantify the research activity in cardiovascular disease (CVD) in the Middle East over the last 10 years. Methods: A Medline search was conducted using medical subject headings and author affiliation to retrieve research articles published from the Middle East between 2003 and 2012 (inclusive). Results: Middle Eastern countries produced only 3% of the total number of CVD research articles in the world. However, the overall trend showed an increase in the number of articles over the years, mainly from Turkey and Iran. Within this region, the ratio of CVD to non-CVD publications was highest in Qatar (0.23). Lebanon ranked first in the number of CVD publications per million persons (PMP) averaging 194.2 publications PMP and Turkey ranked highest in the number of CVD publications per US

Incidence and risk of heart failure in systemic lupus erythematosus.

1000 gross domestic product (GDP) per capita averaging 954 CVD publications per US