Role of Aspirin for Primary Prevention in Persons with Diabetes Mellitus and in the Elderly.

PURPOSE OF REVIEW: To review the clinical evidence of the effect of aspirin as primary prevention for patients with diabetes mellitus and in healthy elderly. RECENT FINDINGS: Two trials were performed to study these two patient populations: ASCEND showed that the use of low-dose aspirin in persons with diabetes, who did not have prior cardiovascular disease, led to a lower risk of cardiovascular events than placebo (8.5% vs 9.6%, rate ratio 0.88, 95% CI 0.79-0.97; p = 0.01). However, it showed a similar magnitude of increased risk of major bleeding among the aspirin group compared with placebo (4.1% vs 3.2%, rate ratio 1.29, 95% CI 1.09-1.52; p = 0.003). ASPREE showed that the use of low-dose aspirin in healthy elderly did not prolong disability-free survival (21.5% vs 21.2%, HR 1.01, 95% CI 0.92-1.11; p = 0.79); however, the rate of major hemorrhage was higher in the aspirin group than in the placebo group (3.8% vs 2.8%, HR 1.38, 95% CI 1.18-1.62; p < 0.001). Additionally, further analyses of secondary end points of death, cardiovascular disease, and major hemorrhage were also studied. Higher all-cause mortality was seen among healthy elderly who received aspirin compared with placebo (12.7% vs 11.1%, HR 1.14, 95% CI 1.01-1.29) and was primarily attributed to cancer-related deaths. Similar risk of cardiovascular disease was seen among elderly who received aspirin compared with placebo (10.7% vs 11.3%, HR 0.95, 95% CI 0.83-1.08) and resulted in a significantly higher risk of major hemorrhage (8.6% vs 6.8%, HR 1.38, 95% CI 1.18-1.62; p < 0.001). These studies show that the use of low-dose aspirin as primary prevention in patients with diabetes and in the elderly does not have overall beneficial effect compared with its use in secondary prevention. In patients with diabetes without prior cardiovascular disease, the benefits of aspirin use were counterbalanced by the bleeding risk. Additionally, in healthy elderly, the use of aspirin did not prolong disability-free survival and instead led to a higher rate of major hemorrhage.

Hypertension in the Cardio-Oncology Clinic.

As cancer therapies improve, the population of survivors of cancer has increased, and the long-term effects of cancer treatments have become more apparent. Cardiotoxicity is a well-established adverse effect of many antineoplastic agents. Hypertension is common in survivors of cancer, can be caused or worsened by certain agents, and has been shown to increase the risk of other cardiovascular diseases including heart failure. Pretreatment risk assessment and careful monitoring of blood pressure during therapy is essential. Aggressive management of preexisting or incident hypertension in survivors of cancer is paramount to decrease the risk of heart failure and other cardiovascular diseases in these patients.

Metabolic Syndrome in Heart Failure: Friend or Foe?

The interplay between metabolic syndrome (MetS) and heart failure (HF) is intricate. Population studies show that MetS confers an increased risk to develop HF and this effect is mediated by insulin resistance (IR). However, obesity, a key component in MetS and common partner of IR, is protective in patients with established HF, although IR confers an increased risk of dying by HF. Such phenomenon, known as "obesity paradox," accounts for the complexity of the HF-MetS relationship. Because IR impacts more on outcomes than MetS itself, the former may be considered the actual target for MetS in HF patients.

Sacubitril/Valsartan: The Newest Neurohormonal Blocker for Guideline-Directed Medical Therapy for Heart Failure.

The burden of heart failure is projected to increase over the next decade; it is predicted that 1 in every 33 Americans will be affected by heart failure. Given that heart failure currently results in more than 1 million hospitalizations every year and the estimated 5-year mortality is approximately 50%, therapies that will improve survival and the economic burden are urgently needed. It is anticipated that the cost of managing heart failure is going to be approximately $70 billion in 2030. Therefore, the recent addition of the combination of sacubitril/valsartan (LCZ696) to guideline-directed medical therapies should ameliorate this burden.

Management of Cancer Therapeutics-Related Cardiac Dysfunction.

Improvements in detection and treatment of cancer have resulted in a significant increase in cancer survivors. However, cancer survivorship comes with long-term risk of adverse effects of cancer therapies, including cardiomyopathy, heart failure, arrhythmias, ischemic heart disease, atherosclerosis, thrombosis, and hypertension. There is a renewed interest in understanding the pathophysiology of cancer therapeuticserelated cardiac dysfunction. In recent years, efforts have been directed to the management of cancer therapeuticserelated cardiac dysfunction. This article discusses the pathophysiology and molecular mechanisms that contribute to cancer therapeutics-related cardiac dysfunction and presents an napproach to the evaluation and treatment of these patients.

Genetics of Dyslipidemia and Ischemic Heart Disease.

PURPOSE OF REVIEW: Genetic dyslipidemias contribute to the prevalence of ischemic heart disease. The field of genetic dyslipidemias and their influence on atherosclerotic heart disease is rapidly developing and accumulating increasing evidence. The purpose of this review is to describe the current state of knowledge in regard to inherited atherogenic dyslipidemias. The disorders of familial hypercholesterolemia (FH) and elevated lipoprotein(a) will be detailed. Genetic technology has made rapid advancements, leading to new discoveries in inherited atherogenic dyslipidemias, which will be explored in this review, as well as a description of possible future developments. Increasing attention has come upon the genetic disorders of familial hypercholesterolemia and elevated lipoprotein(a). RECENT FINDINGS: This review includes new knowledge of these disorders including description of these disorders, their method of diagnosis, their prevalence, their genetic underpinnings, and their effect on the development of cardiovascular disease. In addition, it discusses major advances in genetic technology, including the completion of the human genome sequence, next-generation sequencing, and genome-wide association studies. Also discussed are rare variant studies with specific genetic mechanisms involved in inherited dyslipidemias, such as in the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme. The field of genetics of dyslipidemia and cardiovascular disease is rapidly growing, which will result in a bright future of novel mechanisms of action and new therapeutics.

Echocardiography and heart failure: a glimpse of the right heart.

The catastrophic consequences for patients in the settings of certain clinical conditions such as acute right ventricular infarction or massive pulmonary embolism with right heart failure illustrate the essential role that the right ventricle plays in sustaining life. With the development of more sophisticated diagnostic imaging technologies at the end of the last century and the dawn of this century, the importance of the right ventricle has been clearly demonstrated. The continued and evolving nature of our understanding of the right ventricle was emphasized in 2006, when the National Heart, Blood, and Lung Institute formed a working group focused on developing a better understanding of the right ventricle in both healthy and disease states. The objective of this review paper is to examine the right ventricle structure and function and describe the role of echocardiography in the evaluation of the right ventricle and right heart failure. Special focus will be on echocardiographic images and major society guidelines.

Reversible cardiomyopathy in a patient with chronic myelomonocytic leukemia treated with decitabine/cedazuridine: a case report.

BACKGROUND: Hypomethylating agents (HMAs) have shown efficacy in the treatment of hematological malignancies and are indicated for the treatment of chronic myelomonocytic leukemia (CMML). While the HMA decitabine, in its intravenous formulation, has been used since 2006 for the treatment of CMML, use of its oral formulation has been limited by poor bioavailability due to first-pass metabolism by the enzyme cytidine deaminase. The dose of intravenous decitabine is limited by toxicities such as cardiomyopathy and heart failure. Therefore, cedazuridine was developed as an inhibitor of cytidine deaminase. Cedazuridine decreases the first-pass metabolism of oral decitabine allowing therapeutic levels to be achieved at lower doses, and thus, the novel oral combination of cedazuridine with decitabine was developed. While cardiomyopathy and heart failure are well-established adverse effects associated with intravenous decitabine alone, there to our knowledge there have been no documented incidences of reversible cardiomyopathy in the literature or in patients who participated in the phase 2 and phase 3 clinical trials of oral decitabine-cedazuridine. CASE: This case study presents an 85 year-old Caucasian female with CMML who developed cardiomyopathy and heart failure with reduced ejection fraction after completing 5 cycles of therapy with decitabine/cedazuridine. Furthermore, her symptoms and cardiac function recovered upon discontinuation of the drug. CONCLUSIONS: We present an occurrence of reversible cardiomyopathy in a patient who completed 5 cycles of decitabine/cedazuridine, an oral combination therapy developed to enhance oral bioavailability of decitabine thereby limiting its adverse effects. As the decitabine/cedazuridine combination therapy rises in popularity due to its convenient oral formulation, more trials are needed to understand the prevalence of cardiomyopathy with this drug and to discover preventative strategies for cardiotoxic effects.

Acute study of clinical effectiveness of nesiritide in decompensated heart failure: nesiritide redux.

Nesiritide, a synthetic drug form of human B-type natriuretic peptide, is approved for the early treatment of dyspnea in acute decompensated heart failure. Meta-analyses suggested a risk of worsening renal insufficiency and mortality with its use. Therefore, the Acute Study of Clinical Effectiveness in Decompensated Heart Failure (ASCEND-HF) was designed as a prospective, multicenter, double-blind, randomized trial to examine the use of nesiritide in this common, morbid, and often lethal clinical condition. Two coprimary end points, dyspnea and 30-day hospital readmission or death, were chosen to examine symptomatic response and objective outcomes, respectively. Preliminary reports from ASCEND-HF investigators suggest no significant improvement in symptoms or clinical outcomes, although no adverse effect on mortality or renal function was noted. We recommend the continued use of nesiritide in acute decompensated heart failure as an individualized case-based therapy to those patients who meet criteria for treatment and are expected to receive benefit from its use.

Management of COVID-19 in a durable left ventricular assist device recipient: A continuity of care perspective.

COVID-19 is impacting the cardiovascular community both here in the United States and globally. The rapidly emerging cardiac complications have heightened implications for those with underlying cardiovascular disease. We describe an early case of COVID-19 in a left ventricular assist device recipient in the United States. We discuss our clinical management during the initial admission, outpatient management, and a unique complication of this disease over a 40-day disease course.

Medical therapy for rheumatic heart disease: is it time to be proactive rather than reactive?

Rheumatic Heart Disease (RHD) is well known to be an active inflammatory process which develops progressive calcification and leaflet thickening over time. The potential for statin therapy in slowing the progression of valvular heart disease is still controversial. Retrospective studies have shown that medical therapy is beneficial for patients with calcific aortic stenosis and recently for rheumatic valve disease. However, the prospective randomized clinical trials have been negative to date. This article discusses the epidemiologic risk factors, basic science, retrospective and prospective studies in valvular heart disease and a future clinical trial to target RHD with statin therapy to slow the progression of this disease. Recent epidemiological studies have revealed the risk factors associated with valvular disease include male gender, smoking, hypertension and elevated serum cholesterol and are similar to the risk factors for vascular atherosclerosis. An increasing number of models of experimental hypercholesterolemia demonstrate features of atherosclerosis in the aortic valve (AV), which are similar to the early stages of vascular atherosclerotic lesions. Calcification, the end stage process of the disease, must be understood as a prognostic indicator in the modification of this cellular process before it is too late. This is important in calcific aortic stenosis as well as in rheumatic valve disease. There are a growing number of studies that describe similar pathophysiologic molecular markers in the development of rheumatic valve disease as in calcific aortic stenosis. In summary, these findings suggest that medical therapies may have a potential role in patients in the early stages of this disease process to slow the progression of RHD affecting the valves. This review will summarize the potential for statin therapy for this patient population.