Guilherme H. Oliveira

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.

Long-term mortality after cardiac allograft vasculopathy: implications of percutaneous intervention.

OBJECTIVES This study compared the prognosis of patients with proximal cardiac allograft vasculopathy (CAV) treated with percutaneous intervention (PCI) to the prognosis of those with severe CAV not amenable to PCI. BACKGROUND CAV is a progressive form of arterial narrowing affecting patients with orthotopic heart transplants (OHTs). PCI has been used to treat patients with focal CAV, but its efficacy remains unclear. METHODS Of 853 patients undergoing OHT and subsequent coronary angiographies at the Cleveland Clinic, all patients with at least moderate CAV (>30%) on any coronary angiogram following OHT were included. Of remaining patients with no/mild CAV, 200 patients were randomly chosen to represent the comparison group. All angiograms of the included patients were reviewed and graded according to the International Society of Heart and Lung Transplantation (ISHLT) nomenclature. RESULTS Of the 393 included patients, 100 patients underwent definitive intervention for CAV. Of these 100 patients, 90 patients underwent PCI only, 6 patients underwent coronary artery bypass grafting, and 4 patients underwent repeat OHT. We observed a progressive increase in long-term mortality with worsening CAV. Patients with ISHLT grade 3 CAV had the highest long-term mortality compared with other groups. In addition, there was a significant reduction in the risk for mortality at 2-year follow-up (adjusted odds ratio: 0.26; 95% confidence interval [CI]: 0.08 to 0.82) and 5-year follow-up (adjusted odds ratio: 0.28; 95% CI: 0.09 to 0.93) after PCI compared with patients diagnosed with ISHLT grade 3 CAV, who were deemed unsuitable for PCI. Furthermore, statin use was associated with a significant survival benefit in patients with CAV (hazard ratio: 0.21; 95% CI: 0.07 to 0.61). CONCLUSIONS Worsening severity of CAV was associated with progressively worse long-term survival among heart transplant recipients. Among patients with CAV, long-term survival in those with CAV amenable to PCI was greater than that in those with severe CAV not treatable with PCI.

Maximizing anthracycline tolerability in hematologic malignancies: Treat to each heart's content

Anthracyclines are the cornerstone of therapy for a wide spectrum of malignancies and have improved patient survival. Concern for anthracycline-related cardiotoxicity often leads to dose reductions or use of second-line regimens, which may adversely impact survival. Development of cardiotoxicity depends on a combination of cumulative dose modulated by individual patient characteristics, which we have termed individual cardiotoxic threshold (ICT). Patients with cancer often have characteristics such as age, gender, genetic predisposition and preexisting cardiovascular disease that can potentiate cardiotoxicity. Specialty cardiovascular assessment, more sensitive monitoring technology, and timely interventions in selected patients can decrease cardiotoxicity and improve patient outcomes. Prophylaxis with cardioprotective agents and other strategies have shown promising results in randomized trials and may improve tolerance to anthracyclines. In this review we introduce the concept of ICT and critically analyze the evidence supporting existing strategies to modulate it and increase cardiovascular tolerability of anthracyclines.

Incidence and trends of cardiovascular mortality after common cancers in young adults: Analysis of surveillance, epidemiology and end-results program

AIM To describe the incidence of cardiovascular mortality (CVM) in survivors of major cancers and identify its trends over the past two decades. METHODS We used the surveillance, epidemiology and end-results 19 registry to identify young adults (20-49 years), diagnosed with the following major primary cancers: Lung, breast, liver/intrahepatic bile duct, pancreas, prostate, colorectal, and ovarian from 1990 through 2012 and identified the cumulative incidence of CVM after adjusting for confounding factors. RESULTS We identified a total of 301923 cancers (breast 173748, lung 38938, colorectal 31722, prostate 22848, ovary 16065, liver 9444, pancreas 9158). A total of 2297 (0.8%) of patients had incident CVM. Lung (10-year cumulative CVM 2.4%) and liver (1.73%) cancers had the highest incidence of CVM, while breast (0.6%) and prostate (1.2%) had the lowest CVM mortality, even after multiple adjustments (P < 0.001). Overall, there was a significant improvement in CVM since 1990 [2005-2012 vs 1990-1994, adjusted HR 0.63 (0.54-0.72), P < 0.001]. This was driven by improvements in CVM in lung cancers (P = 0.02), breast (P < 0.001), and a trend in ovarian cancer (P = 0.097). There was no statistically significant improvement in CVM among survivors of colorectal, pancreatic, liver, or prostate cancers. CONCLUSION The risk of CVM differs among different cancers, and is highest among survivors of lung and liver cancers. The incidence of CVM has decreased over the past 2 decades mainly among survivors of lung and breast cancers.

First-in-Human Experience With Transcatheter Mitral Valve-in-Valve Implantation During Left Ventricular Assist Device Placement

Valvular disease is common in patients undergoing left ventricular assist device (LVAD) implantation. Concomitant valve surgery increases procedural complexity and cardiopulmonary bypass time and may lead to worse outcomes.1 Although mitral regurgitation is the most common mitral valve dysfunction in patients undergoing LVAD implantation, mitral stenosis (MS) is occasionally encountered. MS can lead to restricted LVAD flow; therefore, mitral valve replacement is considered to be reasonable in patients with hemodynamically significant MS undergoing LVAD implantation. We describe a successful transcatheter mitral valve replacement (TMVR) via a transapical approach with concomitant LVAD implantation in a patient with bioprosthetic MS. Our patient is a 67-year-old male with ischemic cardiomyopathy, stage D heart failure with reduced ejection fraction, and left ventricular ejection fraction 15%. He had prior 6-vessel coronary artery bypass grafting, bioprosthetic mitral valve replacement (Medtronic Mosaic porcine mitral valve, 29-mm size) for severe mitral regurgitation, and a modified endoventricular circular patch plasty (Dor procedure) for left ventricular aneurysm repair. He had cardiac resynchronization therapy and defibrillator therapy and was paced 99% but remained symptomatic with low output symptoms, as confirmed by hemodynamic assessment. By the time of referral to our institution, he had been hospitalized multiple times in the preceding 6 months with acutely decompensated heart failure, severe ascites, and malnutrition and was maintained on home inotropic therapy with Milrinone at …

Successful use of palliative inotrope therapy in end-stage cardiac ATTR amyloidosis

Patients with heart failure (HF) due to senile (wild type, wt) transthyretin amyloidosis have an overall poor prognosis and are not usually candidates for advanced therapies including heart transplantation (HT) or left ventricular assist devices (LVAD). In these patients, the use of inotropic therapy has not been studied. In this case report, we describe the successful use of chronic palliative inotrope therapy using home milrinone in a patient with end-stage ATTRwt amyloidosis for over two years. Our patient is a 77-year-old man who was newly diagnosed in February of 2014 with atrial fibrillation and heart failure with left ventricular ejection fraction (EF) 20–25% at the time of diagnosis. A nuclear stress test was negative for ischaemia. Cardiac magnetic resonance imaging (MRI) showed diffuse dilatation of all four chambers with myocardial enhancement in a non-coronary pattern highly suggestive of an infiltrative process. Endomyocardial biopsy was consistent with amyloid deposition. Genetic testing revealed age-related senile1 wild-type transthyretin amyloidosis (ATTRwt). He was initially managed medically with metoprolol for rate control of his atrial fibrillation and furosemide. An angiotensin-converting enzyme inhibitor was not used due to his chronic renal disease and fluctuating renal function. He remained in New York Heart Association (NYHA) Class II HF. However, he progressively declined and was admitted a year after initial diagnosis with cardiogenic shock. He was initiated on intravenous milrinone for inotropic support, titrated to 0.25mcg/kg/min. Milrinone was selected over dobutamine due to its longer half-life, and its attribute of increasing the heart rate to a lower extent as compared to dobutamine [1]. The patient was also cardioverted successfully; however, he reverted back to atrial fibrillation soon after. He was initiated on amiodarone; however, he developed bradycardia and it was discontinued along with his beta blocker. Given his age and advanced amyloidosis, he was deemed not to be a candidate for a HT or LVAD. He was discharged home on continuous palliative home milrinone at 0.25mcg/kg/min. He was started on hydralazine and isosorbide mononitrate. An implantable cardioverter defibrillator (ICD) was not implanted given his inotrope dependence. He continues to live on palliative home milrinone currently, two years since its initiation. He has been in permanent atrial fibrillation, but his heart rates uptrended to 140–150 bpm a year ago; hence, he was cautiously reinitiated on amiodarone. He remains NYHA Class III, able to perform his activities of daily living independently and with an acceptable quality of life. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on heart failure recommend the use of chronic inotropic therapy as a bridge to cardiac transplantation or mechanical circulatory support (class IIa), or as palliative therapy in patients with stage D heart failure not eligible for mechanical support or transplant (IIb). The use of chronic inotropic therapy has been associated with increased mortality felt to be secondary to an increased burden of ventricular arrhythmias [2]. However, inotropes are routinely used for bridging advanced HF patients to LVAD or transplant, with survival exceeding 90% [3]. ATTRwt amyloidosis generally carries a better prognosis than HF due to AL amyloidosis [4]. Our patient however declined rapidly within a year of diagnosis, eventually admitted with refractory heart failure and cardiogenic shock. Despite significant advances in heart failure therapy including the development of ICDs and LVADs, survival remains relatively suboptimal in patients with amyloidosis [5]. Heart transplantation (HT) and LVAD implantation for patients with amyloid cardiomyopathy have been studied in a few small studies: 1and 2-year survival rates were 86%, and 86% in the HT group [4] and 55% and 44% in the LVAD study [5], respectively. Our patient had an outcome on home milrinone comparable to similar patients undergoing HT or LVAD placement. We used amiodarone for heart rate control in this patient on milrinone with atrial fibrillation. The use of amiodarone is associated with an increased risk of developing heart block in patients with amyloidosis, as compared to patients without amyloid disease, indicating the need for caution and risk/benefit analysis when using amiodarone in these patients [6]. Any therapy that provides symptomatic benefit in advanced heart failure is important and should be considered for palliative purposes. Despite being associated with worse long-term outcomes, inotropic agents do provide symptomatic and likely survival benefit in advanced heart failure patients who are not candidates for LVAD support. This case highlights the successful use of palliative home milrinone for end-stage HF due to advanced cardiac amyloidosis to improve quality and quantity of life, and should be considered prior to adopting hospice.

Contemporary clinical trial updates in heart failure.

Purpose of review Heart failure is a major source of cardiovascular morbidity and mortality worldwide. The field has benefited from steady progress, and there are now multiple strategies – medical and surgical – to improve cardiovascular outcomes. The quest continues for enhanced pathophysiologic insights and therapies. Recent findings The chosen studies highlight new ways of treating heart failure with reduced ejection fraction (HFrEF) with pharmacotherapy such as sacubitril/valsartan and explore the role of antimicrobial therapy for chronic Chagas’ cardiomyopathy. The role of iron supplementation, spinal cord stimulation and gene therapy are evaluated. The treatment of heart failure with preserved ejection fraction (HFpEF) is scrutinized, and the role of nitrates is discussed. The use of left ventricular assist devices in wider populations of HFrEF patients is considered. Summary These pivotal contemporary trials will impact bedside management. Sacubitril/valsartans mortality benefit in HFrEF and the negative effect of nitrates in HFpEF provide novel insights. Progress with durable mechanical circulatory support and nonpharmacological approaches to heart failure management expand therapeutic options.

Cardiovascular mortality among 76 864 survivors of childhood cancers in the United States: a report from the surveillance, epidemiology, and end-results program

Childhood cancer survivors have increased risk for cardiovascular disease. We sought to describe the trends of cardiovascular mortality (CVM) among survivors of childhood cancers in the United States. We used the Surveillance, Epidemiology, and End-Results 18 database to identify all children who were diagnosed with childhood cancers between 1973 and 2013. We describe the incidence of CVM in four eras (era 1: 1973–1982, era 2: 1983–1992, era 3: 1993–2002, and era 4: 2003–2013). Incidence of CVM was adjusted for baseline characteristics using Cox proportional hazard models. We identified 76 864 childhood cancer survivors. Median age (25th–75th percentile) at diagnosis was 8 (3–14) years; 54% were men and 80% White. Leukemias (29%), lymphomas (13%), and brain malignancies (19%) were the most common cancers. At a median follow-up of 6.3 years, 283 died of cardiovascular causes. Compared with patients diagnosed with cancer in era 1 (1973–1982), CVM was lower in patients diagnosed in era 3 [hazard ratio 0.44 (0.30–0.65), P < 0.001] and era 4 [Hazard ratio 0.31 (0.20–0.47), P < 0.001]. Risk of CVM also increased with age at diagnosis [Hazard ratio 1.04 (1.02–1.06) per year, P < 0.001], and was higher among men [Hazard ratio 1.37 (1.08–1.74), P = 0.01] compared with women. Radiation was associated with increased risk of CVM after adjusting for age, sex, race, year of diagnosis, and type of cancer [Hazard ratio 1.43 (1.11–1.86), P = 0.006]. In this large cohort of childhood cancer survivors, there seems to be a significant decrease in CVM among survivors over the past four decades. Age at diagnosis, male sex, and radiation therapy seem to be associated with increased CVM risk.

Preoperative MELD-XI is not Associated with Mortality after LVAD

Background Kidney and liver dysfunction are common in patients with advanced heart failure undergoing left ventricular assistant device (LVAD) implantation. We have previously shown that Model of End-Stage Liver Disease excluding INR (MELD-XI) scores can predict poor outcomes after heart transplantation. Whether MELD-XI predicts outcomes after LVAD implantation is not well understood. Methods All patients who underwent LVAD implantation at a tertiary referral center (2007-2017) were included and preoperative MELD-XI was calculated. Cox proportional hazard models and Kaplan Meier method were used to describe association with overall post-implant mortality. Penalized smoothed splines were used to visualize the association between continuous MELDXI and mortality. Results A total of 94 patients were included. Mean age was 60±13 years, 78% males, 64% Caucasian, 76% had the HeartMate II. Median MELD-XI was 12.4(9.9-15.9). At a median follow-up of 2.8 years, 31 patients died. There was no difference between patients with MELD-XI >12.4 and MELD-XI ≤12.4 in overall mortality ( P =0.14), figure (panel A). There was no association between continuous MELD-XI and mortality (HR 1.04; 95% CI: 0.96-1.13, P =0.32), figure (panel B). Conclusion Our findings showed that MELD-XI is not associated with mortality after LVAD implantation. These findings need to be validated in a larger group registry to identify best bridging strategy in patients with advanced heart failure and combined kidney-liver dysfunction.

NATIONWIDE DIFFERENCES IN THE UTILIZATION OF MECHANICAL CIRCULATORY SUPPORT AS BRIDGE TO TRANSPLANTATION IN THE UNITED STATES

Mechanical circulatory support devices (MCS) emerged as alternative therapies to heart transplantation given organ shortage. We hypothesized that MCS use varies by state, and is higher in areas with longer waiting times and high wait-list mortality. We queried the UNOS database for all adult heart