Use of Sodium–Glucose Cotransporter 2 (SGLT-2) Inhibitors Beyond Diabetes: On the Verge of a Paradigm Shift?

The sodium–glucose co-transporter 2 (SGLT2) inhibitors have proven effective in glycemia control in patients with type 2 diabetes (T2D) by increasing urinary glucose excretion. However, the beneficial effects of SGLT2 inhibition extend beyond glycemic control, with new studies demonstrating beneficial effects that lead to improved cardiovascular (CV) (cardioprotection) and renal outcomes (renoprotection) in patients with T2D. Pivotal CV outcomes trials have demonstrated a 27-35% reduction in heart failure (HF) hospitalizations in patients with T2D. Importantly, a variety of pleiotropic effects of these new agents have been identified that include, but are not limited to, anti-atherosclerotic, anti-inflammatory, and anti-oxidant effects, decreased vascular stiffness and improved endothelial function, weight loss, reduction in sympathetic activity and in cardiac arrhythmogenesis. Ongoing studies are investigating these actions in patients with and without diabetes. Such results, if positive, may lead to a paradigm shift in the management of CV, renal and even other diseases beyond diabetes. Rhythmos 2020;15(1):67-71

Hybrid Heart Failure Treatment

A case of refractory heart failure (HF) is presented in a 64-year-old gentleman with ischemic cardiomyopathy and severe left ventricular dysfunction, who availed himself of currently available hybrid HF treatment, like optimal medical treatment, electrical and interventional therapies comprising drugs, an implantable cardiac resynchronization therapy defibrillator (CRT-D) effected via alternate route (middle cardiac vein) for left ventricular lead placement combined with percutaneous mitral valve therapy (MitraClip) that prolonged his life to ~10 years. Rhythmos 2021; 16(1):99-101

Micro RNAs: a Revolutionary Discovery in Biology

MicroRNAs (miRNAs) are endogenous, single-stranded, short, noncoding ribonucleic acids (RNAs), which can bind to their target messenger RNAs (mRNAs), leading to the inhibition of translation or degradation of the mRNA. Only recently have scientists discovered the important role that miRNAs play in gene regulation. To date, more than 700 miRNAs have been identified from the human genome. Malfunctioning miRNAs have been implicated in a number of diseases, due to their regulatory functions in transcription, signal transduction, cell cycle regulation, proliferation, cell growth and metabolism, cell apoptosis, and neurogenesis. Absence of miRNAs or their mutations, detected by genetic analysis, has been associated with a broad spectrum of disease processes, such as various cancers and autoimmune, cardiovascular, infectious, metabolic, neurodegenerative, skin, and psychiatric diseases. The large progress made in understanding miRNAs also points to their great potential as new biomarkers in the diagnosis and early detection of various diseases, as well as their promising role in future therapeutics

Therapeutic Intervention in Acute Ischemic Stroke: a Paradigm Shift

Strokes are classified as ischemic or hemorrhagic. Acute ischemic strokes (AIS) are more common than hemorrhagic and they refer to thrombosis or embolism. They are classified into large artery infarctions, small vessel or lacunar infarctions and cardioembolic infarctions. As timely restoration of blood flow (reperfusion) using thrombolytic therapy or percutaneous intervention is the key and most effective strategy for salvaging ischemic myocardial tissue in acute myocardial infarction, the same principle applies to AIS. There is a narrow therapeutic window during which this can be accomplished, since the benefit of reperfusion continually decreases over time. During the acute phase of ischemia, be it myocardial or cerebral, a rapid determination and triaging of patients who are eligible for reperfusion is key to the success of such a salvaging strategy (... excerpt

New Oral Anticoagulants Poised to Usurp the Throne of Vitamin K Antagonists After Over Half a Century

Only after the elapse of over half-a-century of warfarin's reign are we witnessing significant progress in anticoagulation therapy with the advent of new anticoagulants with predictable pharmacologic profile obviating the need for the routine and burdening coagulation monitoring unlike therapy with vitamin K antagonists. Furthermore, these novel agents are devoid of any food interactions and have limited drug-drug interactions since they are minimally metabolized via the cytochrome P450. These unique pharmacokinetic properties have ushered in a new era in anticoagulation therapy with the continuing development of specific direct factor IIa (thrombin) and factor Xa inhibitors. An overview of these novel anticoagulant agents is herein attempted

Sugary Beverages Pose Significant Risks to Cardiovascular and Overall Health

Consumption of added sugar is associated with weight gain and metabolic syndrome, but most importantly with cardiovascular disease (CVD) morbidity and mortality. Sugar-sweetened beverages (SSBs) in the form of soft drinks or sodas constitute a major source of added sugar with its attendant ill effects on health. Of particular concern is the rising consumption of soft drinks among young people. The World Health Organization (WHO) recommends the reduction of free sugars to <10% of total energy intake due to their potential implications in dental caries, weight gain and CVD consequences, however, adherence to this recommendation is generally very low. Non-caloric drinks in the form of artificially sweetened beverages (ASBs) (diet sodas) are popular as alternatives to SSBs. However, these sweeteners may also have various negative, albeit at a lesser degree, health outcomes, including weight gain, obesity, metabolic syndrome, type II diabetes, and CV events. Finally, substantially lower health risks are incurred from 100% fruit juice consumption compared with SSBs. All these issues are herein reviewed and measures are discussed to lessen the consequences of such an unhealthy dietary behavior. Rhythmos 2019;14(3):45-50

Totally Implantable Artificial Heart: Still a Major Challenge

The first mechanical heart was placed by Liotta and Cooley in 1969 in a dying patient at the Texas Heart Institute in Houston as a 2 ½-day bridge for a transplant, albeit the patient died 32 hours after transplantation.1 Years later (1982) a totally implantable artificial heart (model Jarvik-7) was permanently implanted in a patient by DeVries et al at the University of Utah Medical Center in Salt Lake City, Utah, USA and the patient lived for 112 days.2 Subsequent attempts of implantation of a total artificial heart (e.g. CardioWest/SynCardia models) have limited its use as a bridge to transplantation, like the left- or bi-ventricular assist devices (VADs).3-7 The SynCardia model (SynCardia Systems Inc., Tuscon, AZ) has been approved for compassionate use by the Food and Drug Administration (FDA) for patients with end-stage biventricular heart failure as a bridge to transplantation since 1985 and has had FDA approval since 2004.3-5 The SynCardia™ total artificial heart, weighing 180 g, providing a stroke volume of 70 cc, is a pneumatically driven, pulsatile system capable of flows of >9L/min. It is indicated for temporary use as a bridge to transplantation in patients with end-stage non-reversible bi-ventricular failure. Currently, the recipients of this device are hospital-bound and attached to a large pneumatic driver. The bridge to transplantation rate has been ~80% in >1100 implants. In 2010, the FDA gave conditional approval for an Investigational Device Exemption clinical study of the portable Freedom driver (SynCardia) (www.syncardia.com)... (excerpt

Air Pollution in the Metropolis: A Lurking Health Trap

Strong evidence has accumulated from epidemiological and observational studies for a close association between several different air pollutants and adverse health effects, particularly for the residents of metropolitan areas. Although our understanding of the pathophysiological mechanisms involved remains incomplete, there are abundant data which link short-term exposure to air pollution, due to high concentrations of particulate and gaseous matter, toxic metals and aldehydes, with a significant increase in acute cardiopulmonary mortality, particularly in certain high-risk subsets of the population and with an acute increase in hospital admissions for cardiovascular and pulmonary diseases. Furthermore, there is also convincing evidence that prolonged exposure to elevated levels of air pollutants is responsible for chronic ill effects that significantly reduce overall life expectancy. Thus, it is of paramount importance for regulatory agencies to force the implementation of relevant regulations and quality standards in order to protect the health of the population at large. Specific guidelines should also apply for activity restriction for vulnerable and high-risk persons, such as the very young and the elderly, and those with known cardiopulmonary disease or diabetes mellitus

Atherosclerosis: an Athero-Thrombo-Inflammatory Disease

Classical risk factors for the development of atherosclerosis include hypercholesterolemia, hypertension, smoking, and diabetes. When the atheromatous plaque erodes or ruptures, local thrombosis develops which leads to partial or complete vessel occlusion with its attendant potentially catastrophic consequences. Thus, the term athero-thrombotic disease has been adopted. However, inflammation is also a major contributor to the initiation and evolution of this process and has not been adequately addressed. The concept that atherosclerosis is an inflammatory disease has caused a paradigm shift in our understanding of its pathogenesis. Recent convincing evidence has accumulated that inflammation plays a fundamental role in atherothrombosis and the associated risk may be equal to that of hyperlipidemia. Based on this concept, new biomarkers and novel anti-inflammatory and immune therapies are being currently tested for managing atherosclerotic cardiovascular disease

Pregnancy and Cardiovascular Disease

The cardiovascular system undergoes significant changes during pregnancy to adapt to and accommodate the increased metabolic demands of the fetus and the mother. These adaptations produce an important hemodynamic burden on patients with underlying heart disease, and confer an increase in morbidity and mortality. Furthermore, pregnancy may cause specific cardiovascular disorders, which can impose a risk to the pregnant woman and to her fetus. It is estimated that in the western world 0.2-4% of all pregnancies are complicated by cardiovascular diseases (CVD). This risk is in the ascending order as the age of first pregnancy is increasing and as the number of cardiovascular risk factors is rising (e.g. smoking, hypercholesterolemia, diabetes, hypertension, obesity). During pregnancy, the most frequent cardiovascular events relate to hypertension (6–8%). On the other hand, in the western world, the most frequent CVD present during pregnancy is congenital heart disease-CHD (circa 75%), while rheumatic heart disease predominates in the other countries (circa 70%) and CHD is seen in ~15%. In pregnant women with heart disease, maternal death is estimated around 1% but it varies depending on the underlying CVD; neonatal complications occur in 20–28% and neonatal mortality ranges between 1% and 4%. In general, CVDs are the most common cause of maternal death during pregnancy in the Western industrialized world.4 Thus, women of child-bearing age with CVD or cardiovascular risk factors should be counseled and managed early by an interdisciplinary team of gynecologists, cardiologists, and, when necessary, cardiothoracic surgeons... (excerpt