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Sienna Goren,1,* Nermeen Kidwai,1,* Wilbert S Aronow,2 Gregg M Lanier2 1New York Medical College, Valhalla, NY, USA; 2Departments of Medicine and Cardiology, Westchester Medical Center and New York Medical College, Valhalla, NY, USA*These authors contributed equally to this workCorrespondence: Wilbert S Aronow, Department of Cardiology, Westchester Medical Center, and Professor of Medicine, New York Medical College, Macy Pavilion, Room 141, Valhalla, NY, 10595, USA, Tel +1 914 493 5311, Fax +1 914 235 6274, Email Wilbert.Aronow@wmchealth.orgAbstract: Pulmonary arterial hypertension (PAH) is a rare and potentially fatal condition characterized by progressive increases in blood pressure in the arteries of the lungs. Oral selexipag, approved by the Food and Drug Administration (FDA) in 2015 for the treatment of PAH, targets prostacyclin receptors on pulmonary arterial vascular smooth muscle and endothelial cells to improve blood flow through the lungs and reduce pulmonary vascular resistance. Oral selexipag is effective, but may be discontinued due to factors like side effects, emergency conditions, or inability to take oral medication, potentially leading to severe adverse events, such as rebound pulmonary hypertension and right heart failure. To address treatment interruptions, intravenous (IV) selexipag was introduced as an alternative for patients who are temporarily unable to take oral medications. IV selexipag bypasses hepatic metabolism, requiring a 12.5% higher dose compared to the oral form to achieve similar therapeutic effects. It is administered via IV infusion twice daily over 80 minutes, typically for short-term use. However, caution is needed when prescribing selexipag to patients with hepatic or renal issues, and it is contraindicated with strong CYP2C8 inhibitors. A Phase III clinical trial confirmed that switching between oral and IV selexipag was safe, with comparable efficacy and tolerability, though it was limited by small sample size and short duration. Given the risks of treatment interruption and the complexity of managing PAH, this review provides essential insights into the practical use of IV selexipag as a bridging therapy. Furthermore, it calls for larger clinical trials to refine dosing strategies, explore long-term outcomes, and identify patient populations most likely to benefit from IV selexipag.Plain Language Summary: Pulmonary arterial hypertension (PAH) is a rare and dangerous condition that causes high blood pressure in the arteries of the lungs, leading to right heart failure and potentially death. Selexipag is a medication used to treat patients with PAH by widening the blood vessels in the lungs. However, some patients may not be able to take oral selexipag as prescribed, which can worsen their condition. In 2021, an intravenous (IV) form of selexipag was approved as a temporary alternative for these patients. This review examines available literature to provide background and practical instruction for providers prescribing IV selexipag.Unlike oral selexipag, which is processed by enzymes in the liver, the IV form bypasses liver metabolism and enters the bloodstream directly. As a result, the IV dose is typically 12.5% higher than the oral dose to achieve the same therapeutic effects. IV selexipag is administered twice daily through an infusion lasting about 80 minutes and is intended for temporary use. Healthcare providers should use caution when prescribing selexipag to patients with liver or kidney issues. Additionally, selexipag should not be used with medications that block CYP enzymes. A phase III clinical trial reports that common side effects of the IV form of selexipag include headaches and irritation at the injection site. While IV selexipag is considered safe and effective for short-term use, larger studies are needed to better understand how to manage transitions between oral and IV forms.Keywords: prostacyclin, right heart failure, treatment interruption, intravenous selexipag, IP agonist

Eugene Pashkovetsky, Chhaya Aggarwal Gupta, Wilbert S AronowDivision of Cardiology, Department of Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY 10595, USAAbstract: Published data have shown potential advantages of levosimendan in the management of acute decompensated heart failure and advanced heart failure when standard medical therapies threaten hemodynamics and organ perfusion are unable to alleviate clinical symptoms. Levosimendan distinguishes itself from other catecholaminergic inotropes by its three mechanisms of action: positive inotropy, vasodilation, and cardioprotection. In addition, its pharmacokinetics allow for a longer duration of action from the metabolite OR1896 allowing for further cardiovascular therapeutic effects for several days, even after discontinuation of the parent drug.Keywords: levosimendan, heart failure, inotropic therapy

Dipak Chandy,1 Wilbert S Aronow,2 Maciej Banach3 1Division of Pulmonary, Critical Care and Sleep, 2Division of Cardiology, Department of Medicine, New York Medical College, Valhalla, NY, USA; 3Department of Hypertension, Medical University of Lodz, Lodz, Poland Abstract: Systemic hypertension and chronic obstructive pulmonary disease (COPD) frequently coexist in the same patient, especially in the elderly. Today, a wide variety of antihypertensive drugs with different mechanisms of action are available to the prescribing physician. In addition, combination drugs for hypertension are becoming increasingly popular. Certain antihypertensive drugs can affect pulmonary function. Therefore the management of such patients can present therapeutic challenges. We have examined the literature pertaining to the use of antihypertensive drugs in patients with systemic hypertension and coexisting COPD. Although data are often limited or of poor quality, we have attempted to review and then provide recommendations regarding the use of all the specific classes of antihypertensive drug therapies including combination drugs in patients with COPD. The antihypertensive agents reviewed include diuretics, aldosterone receptor blockers, beta blockers, combined alpha and beta blockers, angiotensin-converting enzyme inhibitors, angiotensin II antagonists, calcium channel blockers, alpha-1 blockers, centrally acting drugs, direct vasodilators, and combinations of these drugs. Of these classes, calcium channel blockers and angiotensin II antagonists appear to be the best initial choices if hypertension is the only indication for treatment. However, the limited data available on many of these drugs suggest that additional studies are needed to more precisely determine the best treatment choices in this widely prevalent patient group. Keywords: blood pressure, hypertension, COPD, treatment, antihypertensive drugs

Recent studies indicate that right ventricular performance is impaired even in uncomplicated systemic hypertension. Because of widespread use of beta-blockade in essentially hypertension, it is possible that such treatment often further depresses right ventricular contractility. To test this premise, and to evaluate the changes induced by different beta-adrenoceptor blocking agents on the contractility of right ventricular myocardium, 20 patients with essential hypertension were divided into two groups on a double-blind randomised basis, and maintained on oral oxprenolol or propranolol for five weeks. Cardiac catheterisation and right ventricular cineangiography were performed at the beginning and again at the end of the five week period. Right ventricular end-diastolic volume index did not change significantly in either group. In contrast, right ventricular end-systolic volume index increased, and right ventricular ejection fraction significantly decreased after chronic beta-blockade. Cardiac index decreased in both groups, but these changes were not statistically significant. When the intergroup differences were compared for all measured indices none of the changes between the two groups was statistically significant. Despite its intrinsic sympathomimetic activity, oxprenolol therefore impairs right ventricular performance to an extent nearly equal to that of propranolol. Moreover, right ventricular contractility is clearly diminished after the institution of beta-blockade in hypertensive patients--an effect that has until now been thought to be limited to the left side of the heart. Great caution must therefore be exercised when beta-blockade is initiated in patients with severely abnormal right ventricular function, because frank right ventricular decompensation may result.

Oxprenolol is an experimental beta adrenergic blocker with intrinsic sympathomimetic activity. To compare the effects of long-term administration of oxprenolol on hypertension and hemodynamics with the effects of propranolol, 20 patients with essential hypertension were divided in a double-blind random manner into two 10-patient groups and given placebo for 2 wk, followed by equipotent doses of oxprenolol or propranolol for 5 wk and by placebo for another 2 wk. Right heart cardiac catheterization was performed at the beginning and at the end of the 5-wk beta blockade. Heart rates and blood pressures fell markedly with both agents, although standing heart rate was lowered more by propranolol than by oxprenolol. Plasma renin activity was much lower after beta blockade with either drug. There was no correlation between decreases in blood pressure and renin activity. Although during the stress of repeat cardiac catheterization heart rates remained significantly lower than control, the intra-arterial pressures were not altered significantly by oxprenolol or propranolol, nor was there significant change in pulmonary pressure, vascular resistance, or cardiac output. Thus oxprenolol closely parallels the effects of propranolol in essential hypertension. The negative chronotropic action of both drugs is more marked than their antihypertensive activity.

The cardiotoxicity of the tricyclic antidepressants amitriptyline and doxepin were compared in an animal with acute overdose. The mean repetitive extrasystole threshold (RET) decreased 71.5% with amitriptyline and 27.5% with doxepin (mean blood levels 933 ng/ml and 1889 ng/ml). Physostigmine reversed these effects. Sodium bicarbonate had a variable effect on the lowered RET. The toxic arrhythmogenic effects of the tricyclic antidepressants can be measured by RET and are partly autonomic tone manipulation. In the same blood level range, doxepin is less toxic than amitriptyline.

The effect of amitriptyline that leads to ventricular tachycardia was evaluated by the repetitive extrasystole threshold (RET) technique in 18 dogs. The RET was 28.8 +/- 7.9 mamp before and 8.2 +/- 5.3 mamp after amitriptyline, p less than 0.001. Physostigmine, propranolol, sodium bicarbonate, and left stellate ganglionectomy reversed the effect of amitriptyline on RET. We conclude that amitriptyline overdose predisposes to sudden death by lowering the ventricular fibrillation threshold. This cardiotoxic effect is mediated partly through the central nervous system and can be inhibited by increased plasma binding (bicarbonate), cholinergic stimulation (physostigmine), beta adrenergic blockade (propranolol), and sympathetic denervation (left stellate ganglionectomy).

Twenty-one patients with chronic obstructive pulmonary disease were studied with right heart catheterization. The mean pulmonary artery pressure (PAP) was compared with several noninvasive tests. The pulmonary lobar diameter/thoracic ratio correlated with the PAP, r = 0.677, P less than 0.01. The oxygen saturation and pH were used to derive a calculated value for PAP. The calculated PAP correlated with PAP values measured below 40 mm Hg, r = 0.787, P less than 0.01 but correlated very poorly with PAP values measured above 40 mm Hg. The electrocardiogram revealed at least one criterion for right ventricular abnormality in all 18 patients with pulmonary hypertension, but was too nonspecific to correlate with PAP. The hemoglobin concentration did not correlate with PAP. There was such wide variation between the measured PAP and the various noninvasive tests that these noninvasive tests could not be used to accurately predict the PAP in an individual patient.

This article discusses the efficacy, use and adverse effects of antihypertensive drug therapy in older adults. Numerous double-blind, randomized, placebo-controlled studies have demonstrated that antihypertensive drug therapy reduces cardiovascular events in older adults. All antihypertensive drugs may predispose older patients to the development of symptomatic orthostatic hypotension and postprandial hypotension, and syncope or falls. Adverse effects of diuretics, beta-adrenergic receptor antagonists, ACE inhibitors, angiotensin receptor antagonists, calcium channel antagonists, alpha-adrenergic receptor antagonists, centrally acting drugs and direct vasodilators are discussed. The adverse effects depend on the antihypertensive drugs used, the doses used, the co-morbidities present in older patients taking these drugs and drug-drug interactions. [ABSTRACT FROM AUTHOR]

The prevalence of >70% narrowing of 1, 2, or 3 major coronary arteries and of 3 major coronary arteries was investigated in 2,465 patients (1,437 men, 1,028 women; mean age 69 +/- 13 years) with severe, moderate, mild, or no mitral annular calcium (MAC) diagnosed by 2-dimensional echocardiography who underwent coronary angiography for suspected coronary artery disease. Greater than 70% narrowing of 1, 2, or 3 major coronary arteries was present in 259 of 315 patients (82%) with severe MAC (group 1), in 835 of 1,052 patients (79%) with moderate or mild MAC (group 2), and in 756 of 1,098 patients (69%) with no MAC (group 3) (p <0.001 comparing group 1 with group 3 and group 2 with group 3). Greater than 70% narrowing of 3 major coronary arteries was present in 149 of 315 patients (47%) in group 1, in 366 of 1,052 patients (35%) in group 2, and in 325 of 1,098 patients (30%) in group 3 (p <0.001 comparing group 1 with group 3 and group 1 with group 2; p <0.01 comparing group 2 with group 3). In conclusion, MAC is associated with obstructive >or=1-vessel coronary artery disease and with obstructive 3-vessel coronary artery disease. [ABSTRACT FROM AUTHOR]

The prevalence of peripheral arterial disease (PAD) increases with age. PAD in elderly persons may be asymptomatic, may be associated with intermittent claudication, or may be associated with critical limb ischemia. Other atherosclerotic vascular disorders, especially coronary artery disease (CAD), may coexist with PAD. Elderly persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from CAD. Modifiable risk factors should be treated in persons with PAD such as cessation of cigarette smoking and control of hypertension, dyslipidemia, and diabetes. Statins have been shown to reduce the incidence of intermittent claudication and to improve treadmill exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, should be administered to all persons with PAD. Persons with PAD should be treated with angiotensin-converting enzyme inhibitors and also with beta blockers if CAD is present. Cilostazol should be given to persons with intermittent claudication to improve exercise capacity unless heart failure is present. Exercise rehabilitation programs improve exercise time until claudication. Indications for lower extremity angioplasty, preferably with stenting, or bypass surgery are 1) incapacitating claudication in persons interfering with work or lifestyle; 2) limb salvage in persons with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene; and 3) vasculogenic impotence. However, amputation should be performed if tissue loss has progressed beyond the point of salvage, if surgery is too risky, if life expectancy is very low, or if functional limitations obviate the benefit of limb salvage. [ABSTRACT FROM AUTHOR]

Post-JNC VI research continues to indicate that lower BP levels significantly reduce the risk of coronary heart disease and stroke, but this goal is elusive in clinical practice. For best results, individualize treatment for older patients and those with diabetes or cardiovascular disease. [ABSTRACT FROM AUTHOR]