The Discovery Of Omecamtiv Mecarbil

Approximately, 1 of every 500 people is affected with hypertrophic cardiomyopathy, it is important for patients to understand the dynamics of the disease as it could potentially be life threatening. In most cases, the patients quality of life is not affected, but a few will experience symptoms that cause significant discomfort or undetected complications that could lead to sudden cardiac death. With that in mind, it would be beneficial to recognize what it is, specific causes, the steps of diagnoses, and the options for treatment.

Systolic heart failure is characterized by enlarged ventricles that are unable to fully contract to pump enough blood into circulation to adequately perfuse tissues. The enlargement in ventricles is due to an increased end-systolic volume. If the heart is not able to sufficiently pump the expected volume of blood with each contraction, which in a normal healthy heart is 50-60%, there will be a residual volume left in the heart after every pump (Heart Healthy Women, 2012). With the next period of filling, the heart will receive the same amount of blood volume from the atria combined with that residual volume from the previous contraction. This causes the ventricles to have to dilate to accommodate this increase in volume. The dilation causes the walls of the ventricles to stretch and become thin and weak. Also the myocardium, the muscle layer of the heart, will stretch and not be able to adequately make a full and forceful enough contraction to push blood from the ventricles (Lehne, 2010).

As this disease progresses and the workload of the heart is consistently increased, ventricular hypertrophy occurs. At first, the hypertrophied heart muscles will increase contractility, thus increasing cardiac output; however, as hypertrophy of the ventricular myocardial cells continues, it begins to have poor contractility, requires more oxygen to perform, and has poor circulation from the coronary arteries. This can result in heart tissue ischemia and lead into cardiac dysrhythmias (Lewis et al. 2014, 768).

It leads to a reduction in supine and standing blood pressure without a compensatory rise in the heart rate (reflex tachycardia). The effect of a single dose is apparent in 1-2 hours and its peak effect is 3-6 hours. The abrupt cessation of Ramipril does not produce a rapid and extreme rebound increase in blood pressure. Ramipril can be used as a therapy for heart failure as the drug has beneficial effects on cardiac haemodynamics. It results in decreased left and right ventricular filling pressures, reduced total peripheral resistance and increased cardiac

Insufficient cardiac output causes compensatory mechanisms work to improve cardiac output. They include, sympathetic nervous system stimulation, Renin=angiotensin system activation, other chemical responses, and myocardial hypertrophy.

In systolic ventricular dysfunction or systolic heart failure the heart is not able to produce enough output for adequate tissue perfusion. Heart rate and stroke volume produce cardiac output. Contractility, preload, and afterload influence the heart’s stroke volume. These factors are important in understanding the pathophysiologic consequences of this syndrome and possible treatments. Patients with systolic heart failure usually have dilated, large ventricles and impaired systolic function.

Ivabradine has captured the attention of scientists and has opened up new possibilities for the treatment of stable angina and chronic heart failure. Ivabradine is being developed as an anti-angina drug in patients with stable coronary artery disease and was found to reduce heart rate by selectively inhibiting the pacemaker (If) current in the sinoatrial node (Jedlickova et al., 2015). Recent studies have noted how the reduction of heart rate caused by ivabradine has broader implications on heart health, and also how ivabradine can potentially improve cardiovascular disease (CVD) by mechanisms other than heart rate reduction. Studies have also looked at using ivabradine in more than just treating stable chronic angina, but also in other types of CVD and even chest pains. O 'Connor et al., (2016) examined the effects of ivabradine following myocardial infarction in mice and Jedlickova et al., (2015) through studying ivabradine used as an angina treatment in humans, looked at the effects of ivabradine on endothelial function. These studies have highlighted how ivabradine may not only be beneficial as a treatment via heart rate reduction, but also through pleiotropic mechanisms (Heusch and Kleinbongard, 2016). Ivabradine is an important area of research because it can be useful in more than one context.

These stated facts very well implicate an imperative need to investigate promising alternative treatment strategies as well preventive measures. Impairment in cardiac functions, organ (heart) failure or trigger of compensatory mechanisms (hypertrophy, neurohumoral system activation, autokrine, paracrine stimulation, etc) are the result of loss in cardiac myocytes predominantly due to myocardial infarction (Zimmermann and Eschenhagen, 2003). In addition to the traditional treatment of

In the presence of excess T3 and T4, an increase in number as well as affinity of beta-adrenergic receptors in the heart is noted. These receptors facilitate the action of "fight, flight and fright" hormones ( epinephrine, norepinephrine) which are positively chronotropic ( beat faster) and inotropic ( pump harder) to the heart. This may then lead to cardiac failure in older patients.

The second step in managing patients with CHF is using evidence-based treatment options. Beta-blockers have proven to be effective at increasing left ventricular function; however, the majority of patients are not receiving adequate dosages of the medication. According to Driscoll et al

The major causes of diastolic heart failure are hypertension-induced myocardial hypertrophy and myocardial ischemia-induced ventricular transformation (coronary artery disease). Hypertrophy and ischemia cause a decreased ability of the myocytes to actively pump calcium from the cytosol, resulting in impaired relaxation. Some of the other causes are aortic valvular disease and cardiomyopathies. Diabetes can also lead to diastolic heart failure (Huether and McCune 2012). Other risk factors for this disease are chronic kidney disease, obstructive sleep apnea, and older age. There are two types of the heart failure: systolic heart failure and diastolic heart failure. In systolic heart failure, the left ventricle has difficulty contracting and ejecting blood into the circulation, which causes reduced left ventricular fraction. On the other hand, diastolic heart failure has a slow and delayed relaxation and increased chamber rigidity, which then causes inadequate filling of blood and

According to Metra et al. (2011, p. 516), heart failure is one of the leading causes of illness and death in the cardiac disease spectrum; it renders the heart to become an inefficient pump; as a result, the patient’s develops low blood pressure, reduction in cardiac output and decreased perfusion of blood in vital organs. The culmination of these symptoms represents a very sick client who is unable to demonstrate meaningful improvements without the assistance of inotropes. This inotropic agent is Dobutamine. It is designed to help improve the contractility of the heart muscle and at the same time improve the

cause slower heart rates [95]. We cannot rely solely on reduced heart rates only to diagnose CAN because with advanced nerve dysfunction, heart rates can be normal [95] but it persists in higher rates than patients without any diseases [96]. As a result, heart rate cannot be a reliable factor to determine CAN; however, decreased heart rate is the primary manifestation of CAN [95]. CAN is considered as a common chronic complication of diabetes mellitus that threatens life of patients with diabetes [97]. Its worldwide prevalence varies from 1.6% to 90% [98]. Dysfunction of autonomic nerve fibers that regulate heart rate, cardiac output, myocardial contractility, cardiac electrophysiology, blood vessel constriction and dilatation can be defined as CAN [97, 99]. There are many cardiac disorders that are associated with CAN such as resting tachycardia, intraoperative cardiovascular instability, arrhythmias, asymptomatic myocardial infarction and ischemia and increased rate of mortality after myocardial infarction [97, 99]. CAN is diagnosed by several clinical symptoms, such as postural hypotension, dizziness, light headedness, presyncope, syncope and early fatigue and exhaustion during exercise; all of these are demonstrated in later stages [98]. The first finding of CAN is, decreased heart rate variability (HRV), which is a subclinical finding and can be diagnosed through deep respiration [100]. It can occur even in normal heart rate conditions [100]. Increased resting heart

Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.

Atacand HCT (Candesartan celexetil-hydrochlorothiazide) was developed for patients who were unsuccessfully treated with single antihypertensive agents. The proposed benefit is elicited by the drugs action on angiotensin II receptor antagonists, the agent that causes vasoconstriction. Additionally the second ingredient hydrochlorothiazide a diuretic reduces blood pressure by improving the kidneys ability to eliminate salt and fluid from the body (www.centerwatch.com).