Effects of ivabradine on the prevention of intradialytic hypotension in a dialytic patient with heart failure with reduced ejection fraction

A 65-year-old man with a history of heart failure with reduced ejection fraction (HFrEF) and renal failure was admitted due to difficulty in fluid volume control during haemodialysis. He had frequent episodes of intradialytic hypotension (IDH) with presyncope during haemodialysis despite using a vasopressor agent. Before haemodialysis, his blood pressure was 130–150/60–70 mm Hg, and his heart rate was 80–100 beats/min. There were no specific causes of IDH. For refractory IDH, he was treated with oral ivabradine (2.5 mg two times per day), which resulted in reduced heart rate and decreased occurrence of IDH. This is the first report to describe a dialysis case with HFrEF presenting with an elevated heart rate and impaired fluid management as manifested by recurring IDH, which improved after ivabradine treatment. Ivabradine therapy may assist in increasing stroke volume by lowering the sinus heart rate, thus resulting in the prevention of IDH.

Elevated heart rate across cardiovascular continuum and its management

Elevated heart rate in both healthy individuals and patients with coronary artery disease (CAD), acute myocardial infarction (AMI) and heart failure poses a major risk factor for morbidity and mortality. This fact has further been supported by several studies pointing out to elevated resting heart rate as an important marker for this catastrophe necessitating a prompt therapeutic action plan, consisting of early detection and treatment of the risk factors, to achieve ideal heart rates (approximately 60 beats/minute) in patients which could stop or prevent the progression of the cardiovascular disease (CVD) continuum. Lowering heart rate by therapeutic interventions has shown favorable results, but most of the data so far is retrospective and limited to AMI and heart failure with beta-blocker treatment. Addition of newer drugs into the cardiac armamentarium, like ivabradine, a sinus node inhibitor acting by selective heart rate reduction, has shown several beneficial effects in a variety of conditions spanning from stable angina to heart failure. A consensus meeting was held at the national level wherein experts from various parts of the country discussed and reviewed the importance of heart rate lowering across CV continuum and addition of ivabradine for patients with chronic heart failure and chronic stable angina.

Many Drugs of Abuse May Be Acutely Transformed to Dopamine, Norepinephrine and Epinephrine In Vivo

It is well established that a wide range of drugs of abuse acutely boost the signaling of the sympathetic nervous system and the hypothalamic–pituitary–adrenal (HPA) axis, where norepinephrine and epinephrine are major output molecules. This stimulatory effect is accompanied by such symptoms as elevated heart rate and blood pressure, more rapid breathing, increased body temperature and sweating, and pupillary dilation, as well as the intoxicating or euphoric subjective properties of the drug. While many drugs of abuse are thought to achieve their intoxicating effects by modulating the monoaminergic neurotransmitter systems (i.e., serotonin, norepinephrine, dopamine) by binding to these receptors or otherwise affecting their synaptic signaling, this paper puts forth the hypothesis that many of these drugs are actually acutely converted to catecholamines (dopamine, norepinephrine, epinephrine) in vivo, in addition to transformation to their known metabolites. In this manner, a range of stimulants, opioids, and psychedelics (as well as alcohol) may partially achieve their intoxicating properties, as well as side effects, due to this putative transformation to catecholamines. If this hypothesis is correct, it would alter our understanding of the basic biosynthetic pathways for generating these important signaling molecules, while also modifying our view of the neural substrates underlying substance abuse and dependence, including psychological stress-induced relapse. Importantly, there is a direct way to test the overarching hypothesis: administer (either centrally or peripherally) stable isotope versions of these drugs to model organisms such as rodents (or even to humans) and then use liquid chromatography-mass spectrometry to determine if the labeled drug is converted to labeled catecholamines in brain, blood plasma, or urine samples.

Computational Analysis of Haemodynamic Indices in Synthetic Atherosclerotic Coronary Netwroks

Haemodynamic indices are widely used in clinical practice when deciding on a particular type of treatment. Low quality of the computed tomography data and tachycardia complicate interpretation of the measured or simulated values. In this work, we present a novel approach for evaluating resistances in terminal coronary arteries. Using 14 measurements from 10 patients, we show that this algorithm retains the accuracy of 1D haemodynamic simulations in less detailed (truncated) geometric models of coronary networks. We also apply the variable systole fraction model to study the effect of elevated heart rate on the values of fractional flow reserve (FFR), coronary flow reserve (CFR) and instantaneous wave-free ratio (iFR). We conclude that tachycardia may produce both overestimation or underestimation of coronary stenosis significance.

Computational Analysis of Haemodynamic Indices in Synthetic Atherosclerotic Coronary Netwroks

Haemodynamic indices are widely used in clinical practice for deciding on a particular type of treatment. Low quality of the CT data and tachycardia complicate interpretation of the measured or simulated values. In this work, we present a novel approach for evaluating resistances in terminal coronary arteries. Using 14 measurements from 10 patients, we show that this algorithm retains the accuracy of 1D haemodynamic simulations in less detailed (truncated) geometric models of coronary networks. We also apply the variable systole fraction model to study the effect of elevated heart rate on the values of FFR, CFR and iFR. We conclude that tachycardia may produce both overestimation or underestimation of coronary stenosis significance.

Trier Social Stress Test Elevates Blood Pressure, Heart Rate, and Anxiety, But a Singing Test or Unsolvable Anagrams Only Elevates Heart Rate, among Healthy Young Adults

The Trier Social Stress Test (TSST) is a psychosocial stressor that effectively stimulates the stress response but is labor and time intensive. Although other psychological stressors are often used experimentally, none are known to comparably elevate stress. Two stressors that may potentially elevate stress are a singing task (ST) and unsolvable anagrams, but there are not enough data to support their effectiveness. In the current experiment, 53 undergraduate males and females (mean age = 21.9 years) were brought into the laboratory, and baseline blood pressure, heart rate, self-rated anxiety, and salivary cortisol were recorded. Then, participants were randomly assigned to one of three stress conditions: TSST (n = 24), ST (n = 14), or an unsolvable anagram task (n = 15). Stress measures were taken again after the stressor and during recovery. The TSST significantly elevated systolic blood pressure, diastolic blood pressure, heart rate, and self-rated anxiety from pre-stress levels, replicating its stress-inducing properties. However, the ST and unsolvable anagrams only elevated heart rate, indicating that these methods are not as able to stimulate physiological or psychological stress. Overall, results indicate that out of these three laboratory stressors, the TSST clearly engages the stress response over the ST or unsolvable anagrams.