Optimal Medical Therapy for Stable Ischemic Heart Disease: Focus on Anti-anginal Therapy.

Chronic coronary disease (CCD) is a major cause of morbidity and mortality worldwide. The most common symptom of CCD is exertional angina pectoris, a discomfort in the chest that commonly occurs during activities of daily life. Patients are dismayed by recurring episodes of angina and seek medical help in preventing or minimizing episodes. Angina occurs when the coronary arteries are unable to supply sufficient blood flow to the cardiac muscle to meet the metabolic needs of the left ventricular myocardium. While lifestyle changes and aggressive risk factor modification play a critical role in the management of CCD, management of angina usually requires pharmacologic therapy. Medications such as beta-blockers, calcium channel blockers, nitrates, ranolazine, and others ultimately work to improve the mismatch between myocardial blood flow and metabolic demand. This manuscript briefly describes the pathophysiologic basis for symptoms of angina, and how currently available anti-anginal therapies contribute to preventing or minimize the occurrence of angina.

Thrombi straddling patent foramen ovale: A case series with various management strategies.

This case series explores four cases of thrombi straddling patent foramen ovale (TSFO), an exceedingly rare event. The cases are compared regarding their presentations, evaluations, and management strategies including the first documented uses of percutaneous thromboembolectomy for the removal of a TSFO.

Alterations in heart rate variability are associated with abnormal myocardial perfusion.

BACKGROUND: Abnormalities in the autonomic nervous system may occur in ischemic heart disease, but the mechanisms by which they are linked are not fully defined. The risk of cardiac events is increased during morning hours. Studying the contributions of autonomic mechanisms may yield insights into risk stratification and treatment. We hypothesize that autonomic dysfunction, measured by decreased heart rate variability (HRV), associates with abnormal stress myocardial perfusion imaging (MPI). METHODS: We performed a cross-sectional study of the association between abnormal myocardial stress perfusion with HRV using 276 middle-aged veteran twins without known ischemic heart disease. The primary independent variable was cardiac autonomic regulation measured with 24-hour electrocardiogram (ECG) monitoring, using linear and non-linear (multipole density, or Dyx) HRV metrics. The primary outcome was abnormal perfusion (>5% affected myocardium) during adenosine stress on [13N]-ammonia myocardial perfusion imaging with positron emission tomography. RESULTS: The mean (SD) age was 53 (3) years and 55 (20%) had abnormal perfusion. HRV (by Dyx) was reduced during morning hours in subjects with abnormal perfusion. At 7 AM, each standard deviation (SD) decrease in Dyx was associated a 4.8 (95% CI, 1.5 - 15.8) odds ratio (OR) for abnormal MPI. With Dyx < 2.0, the 7 AM OR for abnormal MPI was 11.8 (95% CI, 1.2 - 111.4). CONCLUSIONS: Autonomic dysfunction, measured by non-linear HRV in the morning hours, was associated with an increased OR of abnormal MPI. These results suggest a potentially important role of ECG-based biomarkers in risk stratification for individuals with suspected ischemic heart disease.

Cardiopulmonary Baroreflex Control of Renal Sympathetic Nerve Activity Is Impaired in Dogs With Left Ventricular Dysfunction.

BACKGROUND: Activation of neurohormonal systems contributes to the progression of heart failure (HF). The mechanism(s) whereby these systems become activated is(are) not fully explained. We determined whether vagal cardiopulmonary baroreflex control of renal sympathetic nerve activity is abnormal in dogs with left ventricular (LV) dysfunction in the absence of clinical HF, and the relationship of abnormalities in baroreflexes to the development of the neurohumoral excitatory state. METHODS: LV end-systolic and end-diastolic dimensions (echocardiography), arterial baroreflex sensitivity (slope of ΔRR/Δsystolic BP during phenylephrine or nitroglycerin bolus), and neurohumoral profiles (plasma norepinephrine, renin activity, and arginine vasopressin) were measured serially in conscious dogs (n=24) with progressive LV dysfunction due to rapid ventricular pacing. LV dimensions were used to define groups with mild, moderate, and marked LV dilatation (LVD; increase in LV end-diastolic volume <15%, 15-30%, and >30% of control, respectively). Changes in renal nerve activity (RNA) were recorded in response to increases in pulmonary capillary wedge pressure (PCWP) induced by volume infusion in anesthetized, sinoaortic-denervated dogs. RESULTS: Cardiopulmonary baroreflex sensitivity (slope of %ΔRNA/ΔPCWP) for mild LVD (-17.8%/mmHg) was the same as controls (-17.7%/mmHg). However, the slopes of moderate (-5.8%/mmHg) and severe LVD (-1.9%/mmHg) were decreased significantly compared with controls (P < .05). Arterial baroreflex sensitivity was preserved at all stages of LVD. Plasma norepinephrine, renin activity, and arginine vasopressin remained unchanged after 4, 7, and 11 days of pacing. CONCLUSIONS: Vagal cardiopulmonary baroreflex control of renal sympathetic nerve activity is blunted early in the development of LVD. These abnormalities precede neurohumoral excitation and abnormal arterial baroreflexes and become apparent when LV end-diastolic volume starts to increase.

Denervation of vagal cardiopulmonary receptors by injection of kainic acid into the nodose ganglia in dogs.

We determined if kainic acid, a neuroexcitotoxin, could be used to denervate the cell bodies of cardiopulmonary vagal sensory neurons. Kainic acid (5 microg) was injected into the nodose ganglion of five dogs. Ten to fourteen days following this procedure, these kainic acid-injected dogs were anesthetized and tested for the extent of the deafferentation. Five additional dogs were used as the control group. Heart rate and mean arterial pressure were measured, and a Swan-Ganz catheter was advanced into a branch of the pulmonary artery to measure pulmonary capillary wedge pressure. We recorded renal sympathetic nerve activity from branches of the left renal nerves. Bilateral carotid occlusion increased heart rate and mean arterial pressure in only the denervated group, but sympathetic nerve activity increased significantly in both groups. This demonstrates that the carotid baroreflex is preserved after kainic acid is injected into the nodose ganglia. Volume expansion by use of warmed saline (15 ml kg(-1)) increased pulmonary capillary wedge pressure 5 mm Hg in control and 14 mm Hg in denervated dogs. In control dogs, sympathetic nerve activity decreased by 10% per mm Hg increase in pulmonary capillary wedge pressure while in denervated dogs, it decreased by 2% per mm Hg. This demonstrates that the vagal cardiopulmonary baroreflex is essentially abolished after injection of kainic acid into the nodose ganglia. After opening the chest, acetylstrophanthidin 100 microg was applied directly to the epicardial surface of the left ventricle to activate cardiac vagal afferents. Epicardial acetylstrophanthidin decreased sympathetic nerve activity by 28% in the control group, but resulted in no change in the kainic-acid-injected dogs. This demonstrates that vagal cardiac chemosensitive reflexes are abolished after bilateral injection of kainic acid into the nodose ganglia. At the end of these experiments, we removed the nodose ganglia for histological evaluation. The vast majority of cell bodies in the ganglia from the denervated group appeared injured compared to cell bodies in ganglia that had not been injected, suggesting that the destruction of cell bodies of vagal afferents was responsible for the functional denervation. Our findings are consistent with the interpretation that kainic acid treatment interrupts vagal afferents that meditate reflex responses to epicardial acetylstrophanthidin and to volume expansion.