Prevalence and temporal trends of anemia in patients with heart failure.

BACKGROUND: Anemia is an important comorbidity in heart failure (HF), and it is associated with increased adverse disease experience and mortality. Previous reports have focused mainly on HF presenting in healthcare settings. We, therefore, set out to establish the nationwide prevalence and temporal trends of anemia in community-based patients with HF in the US. AIM: To establish the nationwide prevalence and temporal trends of anemia in community-based patients with HF in the US. DESIGN: The NHANES dataset, conducted by the CDC National Center for Health Statistics was used to collect nationally representative data on the health and nutritional status of the non-institutionalized US population. METHODS: We utilized the National Health and Nutrition Examination data collected over five survey cycles (2007-16). Included were participants aged 20-80 years with self-reported diagnosis of HF. Anemia was defined using 2 sex specific cut offs of 13 and 12 g/dl (cutoff 1), and 12 and 11 g/dl (cutoff 2), for men and women, respectively. The Chi square test was used to compare prevalence across different categories and survey cycles. Data analysis was done using STATA 16 with P-values < 0.05 considered statistically significant. RESULTS: The median hemoglobin in all HF patients was 13.5 g/dl (IQR 12.4-14.5). The prevalence of anemia among community-based patients with HF in the US was 21.34% (cutoff 1) and 9.03% (cutoff 2) and has been stable from 2007 to 2016. The burden of anemia was disproportionately higher in NH Blacks (34.48%, 95% CI 27.12-42.67) and those with BMI < 25 Kg/m2 (17.4%, 95% CI 10.9-26.64). CONCLUSION: The prevalence of anemia in patients with HF in the US is at least 9% and has remained stable over the past decade. This high persistent burden with limited proven interventions should spur further efforts aimed at identifying impactful ways of addressing anemia in patients with HF.

Peripheral arterial disease and abdominal aortic aneurysm in elderly people.

Patients with peripheral arterial disease (PAD) are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from coronary artery disease. Smoking should be stopped and hypertension, dyslipidemia, diabetes mellitus, and hypothyroidism treated. Statins decrease the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in patients with PAD and hypercholesterolemia. The serum low-density lipoprotein cholesterol should be reduced to <70 mg/dL. Antiplatelet drugs such as aspirin or clopidogrel, angiotensin-converting enzyme (ACE) inhibitors, and statins should be given to patients with PAD. Beta blockers should be given if coronary artery disease is present. Cilostazol improves exercise time until intermittent claudication. Exercise rehabilitation programs should be used. Revascularization should be performed if indicated. Patients with an infrarenal or juxtarenal abdominal aortic aneurysm (AAA) measuring 5.5 cm or larger should undergo repair to eliminate the risk of rupture. Patients with an infrarenal or juxtarenal AAA measuring 4.0 to 5.4 cm in diameter should be monitored by ultrasound or computed tomographic scans every 6 to 12 months to detect expansion. Patients with an AAA should undergo intensive risk factor modification, be treated with ACE inhibitors, statins, and beta blockers, and undergo surgery if indicated.

Management of ventricular arrhythmias.

Underlying causes of ventricular tachycardia (VT) or complex ventricular arrhythmias (VA) should be treated if possible. Anti-arrhythmic drugs should not be used to treat asymptomatic patients with complex VA and no heart disease. Beta blockers are the only antiarrhythmic drugs that have been documented to reduce mortality in patients with VT or complex VA. Radiofrequency catheter ablation of VT has been beneficial in treating selected patients with arrhythmogenic foci of monomorphic VT. The automatic implantable cardioverter-defibrillator (AICD) is the most effective treatment for patients with life-threatening VT or ventricular fibrillation. The American College of Cardiology/American Heart Association class I indications for an AICD are discussed. Other indications for an AICD are discussed. Patients with AICDs should be treated with biventricular pacing, not with dual-chamber rate-responsive pacing at a rate of 70/minute. Patients with AICDs should be treated with beta blockers, statins, and angiotensin-converting enzyme inhibitors or angiotensin blockers.

Management of atrial fibrillation in the elderly.

Atrial fibrillation (AF) is associated with a higher incidence of mortality, stroke, and coronary events than is sinus rhythm. AF with a rapid ventricular rate may cause a tachycardia-related cardiomyopathy. Immediate direct-current (DC) cardioversion should be performed in patients with AF and acute myocardial infarction, chest pain due to myocardial ischemia, hypotension, severe heart failure, or syncope. Intravenous beta blockers, diltiazem, or verapamil may be administered to slow immediately a very rapid ventricular rate in AF. An oral beta blocker, verapamil, or diltiazem should be used in persons with AF if a fast ventricular rate occurs at rest or during exercise despite digoxin. Amiodarone may be used in selected patients with symptomatic life-threatening AF refractory to other drugs. Digoxin should not be used to treat patients with paroxysmal AF. Nondrug therapies should be performed in patients with symptomatic AF in whom a rapid ventricular rate cannot be slowed by drugs. Paroxysmal AF associated with the tachycardia-bradycardia syndrome should be treated with a permanent pacemaker in combination with drugs. A permanent pacemaker should be implanted in patients with AF and symptoms such as dizziness or syncope associated with ventricular pauses greater than 3 seconds which are not drug-induced. Elective DC cardioversion has a higher success rate and a lower incidence of cardiac adverse effects than does medical cardioversion in converting AF to sinus rhythm. Unless transesophageal echocardiography has shown no thrombus in the left atrial appendage before cardioversion, oral warfarin should be given for 3 weeks before elective DC or drug cardioversion of AF and continued for at least 4 weeks after maintenance of sinus rhythm. Many cardiologists prefer, especially in older patients, ventricular rate control plus warfarin rather than maintaining sinus rhythm with antiar-rhythmic drugs. Patients with chronic or paroxysmal AF at high risk for stroke should be treated with long-term warfarin to achieve an International Normalized Ratio of 2.0 to 3.0. Patients with AF at low risk for stroke or with contraindications to warfarin should be treated with aspirin 325 mg daily.

Deleterious influence of hypothyroidism on evolving myocardial infarction in conscious dogs.

To study the influence of hypometabolism on evolving myocardial infarction in a model with intact autoregulation, we investigated 53 awake dogs after coronary artery occlusion. Severe hypothyroidism was induced by the intravenous administration of 131I. Animals were instrumented to obtain hemodynamic measurements, and regional myocardial blood flow was measured with radioactive microspheres. Infarct size was determined by the creatine kinase depletion method, and dysrhythmia analysis was performed from 24-h Holter monitor tapes in animals matched for infarct size. The microarchitecture of hypothyroid myocardium was determined by the electron microscope. Before coronary occlusion, mean systemic pressure in hypothyroid dogs was reduced by 14% and cardiac output reduced by 32%, with no change in left ventricular end-diastolic pressure, first derivative of left ventricular pressure rise, (dP/dt), or heart rate. After coronary occlusion, there was deterioration in hemodynamic measurements in both groups, with lower absolute levels of mean systemic blood pressure and cardiac output obtained in hypothyroid dogs. Hypothyroidism was detrimental to evolving infarction with a 36% increase in infarct size present in hypothyroid dogs (30 +/- 2%) compared to euthyroid controls (22 +/- 3%), P less than 0.05. Dysrhythmias were more severe in hypothyroid dogs. There were no changes in the relationship between regional myocardial blood flow and the extent of infarction after coronary occlusion. Abnormalities in microarchitecture were present in hypothyroid dog myocardium. Severe hypometabolism in this model was associated with alterations in hemodynamics, more severe dysrhythmias and changes in microarchitecture. The combined effect of these alterations resulted in an overall detrimental influence of hypothyroidism on evolving myocardial necrosis in this model.

Diagnostic and prognostic significance of exercise-induced premature ventricular complexes in men and women: a four year follow-up.

Two hundred eighty patients (197 men and 83 women) with normal rest electrocardiograms and no history of prior myocardial infarction were referred for evaluation of chest pain. It was found that exercise-induced premature ventricular complexes had a lower sensitivity, specificity, positive predictive value and negative predictive value in predicting significant coronary artery disease than exercise-induced ST segment depression greater than or equal to 1 mm. The incidence of exercise-induced premature ventricular complexes was not significantly different in patients with no significant coronary artery disease, single vessel disease or multivessel disease. The site of origin of exercise-induced premature ventricular complexes was not helpful in predicting the presence or severity of coronary artery disease. At a mean follow-up period of 47.1 months, exercise-induced premature ventricular complexes did not predict coronary events (cardiac death or nonfatal myocardial infarction) in men or women.

Effect of marijuana and placebo-marijuana smoking on psychological state and on psychophysiological cardiovascular functioning in anginal patients.

Ten male anginal patients with angiographically documented coronary artery disease, in a randomized double-blind crossover study, smoked one marijuana cigarette (containing 18 mg of delta-9-THC) on one morning and one placebo marijuana cigarette (containing 0.05 mg of delta-9-THC) on a successive morning. Significant increases occurred in average cognitive and intellectual impairment scores, derived from the objective content analysis of 5 min of speech, 30 mins after smoking the marijuana cigarette as compared to the placebo marijuana cigarette, and these scores decreased to near presmoking levels 60 min after smoking. No significant average changes occurred in anxiety or three hostility scale scores following smoking marijuana. Sizable individual differences were noted in the psychological responses to marijuana smoking due, presumably, to personality differences and/or differences in THC pharmacokinetics. Significant psychocardiovascular hemodynamic correlations, as measured by echocardiography, were observed during placebo-marijuana smoking between hostility inward scores and systolic blood pressure and ejection fraction, overt hostility outward scores and diastolic blood pressure, as well as between anxiety scores and stroke volume and left ventricular end-diastolic dimension and left ventricular diastolic volume. These significant psychophysiologic correlations were all eliminated during marijuana smoking. In view of associated findings that marijuana smoking decreased myocardial oxygen delivery, decreased exercise time until the onset of anginal pain, and increased myocardial oxygen demand in anginal patients, the use of marijuana by such patients is clearly inadvisable.

Effects of oxprenolol and propranolol on systolic time intervals.

Twenty patients with coronary heart disease participated in a double-blind, randomized, crossover study on three study mornings to evaluate the effect of oral oxprenolol 80 mg, oral propranolol 80 mg, and placebo on left ventricular contractility. Systolic time intervals were performed in the control period and at 60, 90, 120, 150, 180, 240, 300, and 360 min after medication. None of 20 patients developed adverse effects. The 80-mg doses of oxprenolol and propranolol had a negative chronotropic effect, with the resting heart rate slightly but consistently decreased more after propranolol, attaining statistical significance at 90, 150, and 300 min. That the 80-mg doses of oral oxprenolol and propranolol also induced a negative inotropic effect was indicated by a similar prolongation of the external isovolumic contraction time and pre-ejection period intervals. This equipotent dose of oxprenolol in producing a negative inotropic effect induces less resting bradycardia than propranolol.

Cardiotoxicity of amitriptyline and doxepin.

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.

Effect of tocainide and quinidine on premature ventricular contractions.

The efficacy on premature ventricular contractions (PVCs) of tocainide 600 mg three times daily and of quinidine sulfate 300 mg four times daily administered for 8 wk versus placebo administered for 6 wk was determined in 41 patients. Neither the subjects nor the interpreter of the Holter recordings knew which medication had been used. Adverse effects occurred in 14 of 22 patients (64%) on tocainide and in nine of 19 (47%) on quinidine. Adverse effects caused 13 of 22 patients (59%) on tocainide and six of 19 (32%) on quinidine to discontinue medication. Reduction of PVCs greater than or equal to 75% over placebo occurred in one of nine patients (11%) on tocainide and in six of 13 (46%) on quinidine. By Lown's classification, a reduction in one grade of PVCs occured in two of nine patients (22%) on tocainide and in eight of 13 (62%) on quinidine. Neither tocainide nor quinidine has a high incidence of efficacy and a low incidence of adverse effects but, in the doses used, quinidine was more effective, benefited a larger proportion of patients, and induced fewer adverse effects than tocainide.

Effect of amitriptyline antidotes on repetitive extrasystole threshold.

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).

Effect of smoking marihuana and of a high-nicotine cigarette on angina pectoris.

The purpose of this study was to determine the effect of smoking marihuana and of high-nicotine cigarettes on exercise-induced angina pectoris. Smoking 1 marihuana cigarette increased the resting product of systolic blood pressure times heart rate 54%, increased the venous carboxyhemoglobin level, and decreased the exercise time until angina 50% in 10 patients with angina pectoris. Smoking 1 high-nicotine cigarette increased the resting product of systolic blood pressure times heart rate 36%, increased the venous carboxyhemoglobin level, and decreased the exercise time until angina 23%. Smoking either marihuana or high-nicotine cigarettes decreases exercise performance until angina by increasing myocardial oxygen demand and by decreasing myocardial oxygen delivery. Smoking 1 marihuana cigarette decreased the exercise time until angina more than smoking 1 high-nicotine cigarette (p less than 0.001).

Effects of acebutolol and propranolol on left ventricular performance assessed by echocardiography.

To assess the effects of acebutolol and propranolol on resting left ventricular function, 21 patients with coronary artery disease were studied. A baseline echocardiogram was obtained on day 1, and in a double-blind, randomized, crossover study the patients received 40 mg propranolo every 8 hr for 1 wk, 300 mg acebutolol every 8 hr for 1 wk, and 1 capsule placebo every 8 hr for 1 wk. On days 8, 15, and 22, after an echocardiogram at 7:30 A.M. (i.e., 7.5 hr after the midnight dose), they received double-blind randomized, crossover medications (acebutolol 300 mg, propranolol 40 mg, or placebo). The echocardiogram was repeated at 1.2, and 4 hr after placebo or propranolol and at 2, 3, and 5 hr after acebutolol. The left ventricular end diastolic dimension, left ventricular end systolic dimension, percent systolic shortening of the left ventricular minor axis, and ejection fraction were determined. We found that there was no significant difference between control values for any of the above parameters and those obtained at 1, 2, 4, or 7.5 hr after propranolol or placebo and at 2, 3, 5, or 7.5 hr after acebutolol. We conclude that in the doses used, acebutolol and propranolol do not induce depression of resting left ventricular function in patients with coronary artery disease who have normal or near normal left ventricular function at rest.

Exercise duration to angina at two and twelve hours after timolol.

Eight patients who improved their exercise duration to angina or marked fatigue (greater than or equal to 25%) on timolol 10 to 30 mg twice daily over that on placebo 8 to 14 mo previously were subjects in a double-blind, randomized, crossover 4-wk study of the effect of timolol on exercise duration 2 and 12 hr after medication. One patient was discontinued from the study because unstable angina developed on placebo. Mean exercise duration on timolol over control was increased at 12 hr (p less than 0.02) and at 2 hr ( p less than 0.001) after drug. There was an increase in exercise duration greater than or equal to 25% on timolol over control compared with placebo in three of seven patients (43%) 12 hr after drug and in seven of seven (100%) 2 hr after drug. Timolol 10 to 30 mg twice daily prolongs exercise duration to angina or marked fatigue at 2 hr after drug and in some responders at 12 hr after drug.

Effect of trimazosin on hemodynamics in chronic heart failure.

The effect of the oral vasodilator trimazosin on hemodynamics in 16 patients with chronic left ventricular failure was compared with placebo in a double-blind, randomized study. Eight patients received trimazosin 100 to 300 mg, and 8 received placebo. Over the 6-hr period after medication trimazosin caused no significant change in heart rate, stroke work index, or pulmonary vascular resistance, but there were significant reductions in mean arterial pressure (p less than 0.05), mean right atrial pressure (p less than 0.01), mean pulmonary artery pressure (p less than 0.01), mean pulmonary capillary wedge pressure (p less than 0.01), and systemic vascular resistance (p less than 0.01), and significant increases in stroke index (p less than 0.05) and cardiac index (p less than 0.05). None of 8 patients improved after placebo, whereas 5 of 8 patients (63%) had a good or excellent hemodynamic response after trimazosin (p = 0.006). Four of 4 patients who received 300 mg of trimazosin had a good or excellent response. Trimazosin is a long-acting orally effective vasodilator which improves ventricular function in patients with left ventricular failure.

Comparison of trimazosin and methyldopa in hypertension.

Eighteen patients with hypertension participated in a double-blind, randomized study to evaluate the effect of trimazosin, methyldopa, and placebo on supine and standing blood pressure and heart rate. Of 6 patients on methyldopa, one developed drug fever (and was dropped from the study) and one developed impotence. None of 6 patients on trimazosin and none of 6 patients on placebo developed any adverse effects. The mean supine blood pressure on 900 mg trimazosin daily was 17.0/12.8 mm Hg lower than that on the first placebo trial (p less than 0.01) and 17.0/12.1 mm Hg lower than that on the second placebo trial (p less than 0.01). The mean supine blood pressure on 2,250 mg methyldopa daily was 17.8/12.4 mm Hg lower than that on the first placebo trial (p less than 0.01) and 16.8/13.0 mm Hg lower than that on the second placebo trial (p less than 0.01). The mean supine blood pressure was not significantly affected by placebo. Trimazosin, 900 mg daily, and methyldopa, 2,250 mg daily, were equally effective in lowering supine and standing systolic and diastolic blood pressure and did not affect supine or standing heart rate.

Effect of acebutolol and propranolol on premature ventricular complexes.

A double-blind, randomized study comparing the efficacy of intravenous acebutolol with propranolol on frequent premature ventricular complexes (PVCs) in 24 patients is reported. Frequent PVCs were abolished or reduced by 75% or more in 10 of 12 patients (83%) given acebutolol and in 10 of 12 patients (83%) given propranolol. The therapeutic effect of acebutolol lasted for at least 1 hr in 4 of 12 patients (33%), for at least 3.5 hr in 3 of 12 patients (25%), and for at least 4 hr in 2 of 12 patients (17%). The effect of propranolol lasted for at least 1 hr in 6 of 12 patients (50%), for at least 3.5 hr in 4 of 12 patients (33%), and for at least 4 hr in 4 of 12 patients (33%). Hence, intravenous acebutolol and propranolol were equally effective.

Effect of tolamolol and propranolol on exercise heart rate and angina.

Fifteen patients with angina pectoris participated in a double-blind study evaluating the effect of intravenous saline, 10 mg of intravenous tolamolol, 20 mg of intravenous tolamolol, and 10 mg of intravenous propranolol on resting and exercise heart rate and on exercise time until angina. Twenty mg of tolamolol and 10 mg of propranolol caused a similar decrease in mean resting heart rate, heart rate after a similar amount of exercise, heart rate at angina, resting product of systolic blood pressure times heart rate, and product of systolic blood pressure times heart rate at angina and were, therefore, judged equipotent. Tolamolol, 10 and 20 mg, and propranolol, 10 mg. were not followed by a significant change in mean exercise duration until angina, but there was a 25 percent increase in exercise time until angina in 4 of 15 patients (27 percent) after 10 mg of propranolol and in 3 of 15 patients (20 percent) after 20 mg of tolamolol.

Effects of isosorbide dinitrate on pulmonary hypertension in chronic obstructive pulmonary disease.

Eighteen patients with chronic obstructive pulmonary disease with pulmonary hypertension were studied to assess the hemodynamic response to acute oxygen administration and to oral isosorbide dinitrate (ISDN). All 18 patients had baseline hemodynamic measurements and hemodynamic measurements during low-flow nasal oxygen. Following a second baseline measurement, patients received either oral ISDN (11 patients) or placebo (7 patients) in a randomized, double-blind protocol. Heart rate decreased with oxygen administration but there were no other significant hemodynamic changes. With oral ISDN, there was a significant fall in pulmonary artery and brachial artery pressure. Cardiac output, right atrial pressure, pulmonary wedge pressure, and pulmonary vascular resistance all fell but not significantly. We conclude that oral ISDN is effective in reducing pulmonary hypertension in patients with chronic obstructive pulmonary disease.

Verapamil in atrial fibrillation and atrial flutter.

A double-blind randomized study was performed to compare the efficacy of intravenous verapamil with saline in 28 patients with a rapid ventricular rate and atrial fibrillation or atrial flutter. Conversion of atrial fibrillation to sinus rhythm occurred in none of 14 patients after saline and in 3 of 20 patients (15%) 7 to 160 min after verapamil. The ventricular rate in atrial fibrillation was slowed greater than or equal to 15% in 2 of 14 patients (14%) by saline, in 17 of 20 patients (85%) by 1 dose of verapamil (p less than 0.001), and in 19 of 20 patients (95%) by 1 or 2 doses of verapamil (p less than 0.001). Conversion of atrial flutter to sinus rhythm occurred in none of 4 patients after saline and in 1 of 7 patients (14%) 105 min after verapamil. The ventricular rate in atrial flutter was slowed greater than or equal to 15% in none of 4 patients by saline, in 4 of 7 patients (57%) by 1 dose of verapamil, and in 7 of 7 patients (100%) by 1 or 2 doses of verapamil (p less than 0.001).