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Biomedical subjects

M Packer

Publications and source records attributed to M Packer.

At least 37 records · Page 2Linked to original sources
PubMed1990

Prognostic importance of the serum magnesium concentration in patients with congestive heart failure.

Magnesium abnormalities are common in patients with congestive heart failure but the clinical and prognostic significance of an abnormal serum magnesium concentration in this disorder has not been investigated. Therefore, the relation between serum magnesium concentration and the clinical characteristics and long-term outcome of 199 patients with chronic heart failure was evaluated. The serum magnesium concentration was less than 1.6 mEq/liter in 38 patients (19%), within the normal range in 134 patients (67%) and greater than 2.1 mEq/liter in 27 patients (14%). Patients with hypomagnesemia had more frequent ventricular premature complexes and episodes of ventricular tachycardia than did patients with a normal serum magnesium concentration (p less than 0.05). Even though the two groups were similar with respect to severity of heart failure and neurohormonal variables, patients with a low serum magnesium concentration had a significantly worse prognosis during long-term follow-up (45% versus 71% 1 year survival, p less than 0.05). Patients with hypermagnesemia had more severe symptoms, greater neurohormonal activation and worse renal function than did patients with a normal serum magnesium concentration but tended to have fewer ventricular arrhythmias. Hypermagnesemic patients had a worse prognosis than did those with a normal magnesium concentration (37% versus 71% 1 year survival, p less than 0.05). In conclusion, the measurement of serum magnesium concentration provides important clinical and prognostic information in patients with chronic heart failure.

Female↗
PubMed1990

Diastolic function as a target of therapeutic interventions in chronic heart failure.

Although conventional wisdom holds that pharmacological interventions improve the haemodynamic and clinical status of patients with chronic heart failure by enhancing systolic performance, this hypothesis fails to explain many of the responses seen following the administration of these drugs. The observation that abnormalities of diastolic function are an earlier and more sensitive marker of heart failure than abnormalities of systolic function suggests that vasodilator and inotropic drugs may act primarily by improving diastolic function. This belief is supported by the following findings: (1) exercise capacity in chronic heart failure is more closely related to left ventricular filling pressure than to cardiac output or limb blood flow; (2) only drugs that lower left ventricular filling pressure have been shown to improve exercise capacity, whereas drugs that primarily increase cardiac output or left ventricular ejection fraction do not enhance effort tolerance; (3) the primary mechanism by which vasodilator and inotropic drugs lower left ventricular filling pressure is by exerting a favourable effect on left ventricular diastolic function rather than on left ventricular volume; (4) drugs that improve diastolic function tend to affect favourably the clinical status of patients with chronic heart failure, whereas drugs that adversely alter ventricular relaxation produce deleterious haemodynamic and clinical effects. These observations suggest that the diastolic abnormalities of heart failure may be an ideal target for the development of new therapeutic interventions.

Cardiac Output, Low↗
PubMed1990

Comparative hemodynamic effects of procainamide, tocainide, and encainide in severe chronic heart failure.

Many of the newer antiarrhythmic agents are said to cause minimal myocardial depression, but their hemodynamic effects have not been invasively evaluated and compared in patients with severe chronic heart failure. In a randomized, crossover study, the hemodynamic responses to single oral doses of procainamide (750 mg), tocainide (600 mg), and encainide (50 mg) given to 21 patients with severe chronic heart failure were compared. Cardiac performance decreased with all three drugs, but the magnitude of deterioration differed among the three agents. Stroke volume index decreased with procainamide (-5 +/- 1 ml/m2, p less than 0.001), tocainide (-7 +/- 1 ml/m2, p less than 0.001), and encainide (-8 +/- 1 ml/m2, p less than 0.001), but the decline was significantly greater with encainide than with procainamide (p less than 0.05). Similarly, left ventricular filling pressure increased with tocainide and encainide (+4 +/- 1 and +5 +/- 2 mm Hg, respectively; both p less than 0.05), but not with procainamide; the increase was significantly greater with tocainide and encainide than with procainamide (p less than 0.001). These deleterious hemodynamic effects were accompanied by worsening symptoms of heart failure in six patients with encainide and seven patients with tocainide but in only two patients with procainamide. Serum levels for all drugs were in the therapeutic range. In conclusion, although the three type I antiarrhythmic agents tested may all adversely affect left ventricular function in patients with heart failure, encainide and tocainide are more likely than procainamide to cause hemodynamic and clinical deterioration.

Aged↗
PubMed1990

Abnormalities of diastolic function as a potential cause of exercise intolerance in chronic heart failure.

Most research in the field of chronic heart failure during the last 20 years has been directed toward defining and understanding the abnormalities of systolic function seen in this disorder, but systolic performance is not a determinant of effort tolerance. Several lines of evidence, however, suggest a strong relation between exercise capacity and abnormalities of diastolic function in chronic heart failure. Of all the commonly measured hemodynamic variables, effort tolerance (whether limited by dyspnea or fatigue) varies more closely with the level of left ventricular filling pressure than the left ventricular ejection fraction. Consequently, drugs that lower ventricular filling pressures are more likely to enhance exercise capacity than drugs that primarily increase cardiac output and left ventricular ejection phase indexes. Vasodilator drugs do not reduce left ventricular filling pressure, however, by simply redistributing central blood volume to the peripheral capacitance circuits because these agents do not predictably decrease left ventricular volumes. Instead, clinically effective drugs seem to reduce left ventricular filling pressure primarily by producing a favorable shift in the left ventricular diastolic pressure-volume relation. Conversely, agents that adversely affect the diastolic pressure-volume relation frequently cause clinical deterioration. These findings suggest that abnormalities of diastolic rather than systolic performance may be the most important determinants of the clinical status and exercise intolerance of patients with chronic heart failure.

Adrenergic beta-Antagonists↗
PubMed1990

Pathophysiological mechanisms underlying the effects of beta-adrenergic agonists and antagonists on functional capacity and survival in chronic heart failure.

Recently completed controlled clinical trials suggest that the functional status and natural history of patients with chronic heart failure can be modified by drugs that enhance or interfere with the effects of the sympathetic nervous system. Long-term treatment with beta-receptor agonists can produce clinical benefits in some patients by improving left ventricular diastolic function, even if tolerance develops to the effects of these drugs on cardiac output and left ventricular ejection fraction. beta-Receptor stimulation, however, may also provoke ventricular arrhythmias by a direct effect on the failing heart or by promoting the development of hypokalemia. Similarly, long-term treatment with beta-receptor antagonists may improve left ventricular systolic performance, ameliorate symptoms, and reduce mortality in chronic heart failure. beta-Receptor blockade, however, may lead to worsening heart failure by interfering with the positive inotropic or the peripheral vasodilator actions of endogenous catecholamines. It is noteworthy that many of the benefits of beta-adrenergic agonists and antagonists seem to be mediated by the effects of these drugs on the beta 1-receptor, whereas many of the deleterious responses to treatment appear to be related to the interaction of these agents with the beta 2-receptor. These observations support the concept that beta 1-receptors are the principal mediators of cardiac sympathetic nerve activity in states of circulatory stress, are most likely to be altered by the abnormal pathophysiological conditions of chronic heart failure, and consequently, provide a rational target for the development of novel therapeutic agents.

Adrenergic beta-Agonists↗
PubMed1990

Due process.

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Attitude of Health Personnel↗
PubMed1989

Adverse hemodynamic and clinical effects of encainide in severe chronic heart failure.

STUDY OBJECTIVE: To evaluate the hemodynamic effects of the antiarrhythmic drug, encainide, in patients with severe chronic heart failure. DESIGN: Unblinded, before-after study. SETTING: Referral center for patients with heart failure. PATIENTS: Thirty patients with severe chronic heart failure and a left ventricular ejection fraction less than 40%. INTERVENTIONS: Invasive hemodynamic measurements were done (using a balloon-tipped thermodilution catheter) before and for 3 hours after a single oral dose of 50 mg of encainide. MEASUREMENTS AND MAIN RESULTS: Ninety to one hundred and twenty minutes after its administration, encainide produced a significant deterioration in cardiac performance, as reflected by a fall in cardiac index from 2.3 to 1.8 L/min.m2 body surface (mean change 0.5 +/- 0.1; P less than 0.001), a fall in stroke work index from 26 to 18 g.m/m2 (mean change 8 +/- 2; P less than 0.001), and an increase in left ventricular filling pressure from 19 to 22 mm Hg (mean change 3 +/- 2; P less than 0.05). These deleterious hemodynamic effects were accompanied by worsening symptoms of heart failure in 8 of the 30 patients. Serum levels of encainide and its metabolites, O-desmethylencainide and 3-methoxy-O-desmethylencainide, were within the therapeutic range in most patients. CONCLUSIONS: Encainide can cause adverse hemodynamic and clinical effects in patients with severe chronic heart failure.

Adult↗
PubMed1989

Effect of phosphodiesterase inhibitors on survival of patients with chronic congestive heart failure.

Controlled and uncontrolled hemodynamic and clinical studies have noted that the long-term treatment of patients with chronic heart failure with phosphodiesterase (PDE) inhibitors, such as amrinone, milrinone, enoximone and imazodan, may accelerate progression of the underlying disease and provoke serious ventricular arrhythmias. However, in an experimental model of chronic progressive left ventricular dysfunction, milrinone has been reported to reduce mortality to a degree comparable to that seen with the converting-enzyme inhibitors. These discordant observations suggest that either the deleterious hemodynamic and electrophysiologic effects of the PDE inhibitors are not translated into an adverse effect on mortality, or the animal model used to evaluate the effects of milrinone cannot be used to investigate the action of these drugs in human heart failure. Unfortunately, no trial has prospectively evaluated the effect of PDE inhibition on the survival of patients with heart failure. To address this need, the Prospective Randomized Milrinone Survival Evaluation (PROMISE Trial) has been launched in 75 to 90 clinical research centers in the United States and Canada. This study will enroll 750 patients with severe (class IV) heart failure, who have symptoms refractory to conventional therapy with digitalis, diuretics, converting-enzyme inhibitor and direct-acting vasodilators. Patients will be randomly assigned to additional treatment with either oral milrinone or placebo, and followed until death or to the conclusion of the study. The primary end point will be all-cause mortality, but the effect of milrinone on functional capacity will also be evaluated. The results of the study should define the place of PDE inhibitors in the treatment of chronic heart failure.

Animals↗
PubMed1989

Does digitalis work in chronic heart failure? The end of a 200-year-old controversy.

Controlled trials using modern methods of assessment in well-defined groups of patients have now convincingly demonstrated that digitalis is an effective and well-tolerated drug in patients with chronic heart failure who have left ventricular systolic dysfunction. These encouraging findings concerning digitalis, however, should not be construed to suggest that the drug should be used alone in the treatment of heart failure. Digitalis cannot adequately control the fluid retention seen in most patients with chronic heart failure; diuretics should be added to maintain sodium balance. Digitalis has not been shown to prolong life in chronic heart failure; converting-enzyme inhibitors should be added to reduce morbidity and mortality. All three drugs should be used together in the management of patients with this disorder.

Chronic Disease↗
PubMed1989

Predictors of total mortality and sudden death in mild to moderate heart failure. Captopril-Digoxin Study Group.

The relation between baseline clinical variables and subsequent mortality was examined in 295 patients with mild to moderate heart failure who participated in a multicenter trial comparing the effect on treadmill exercise tolerance of captopril, digoxin and placebo given in addition to a diuretic drug. At baseline study, all patients had a left ventricular ejection fraction less than or equal to 40%; 81% were in New York Heart Association functional class II. The etiology of heart failure was ischemic in 62% and nonischemic in 38%. During an average follow-up period of 16 months, 47 patients (16%) died and 24 deaths were classified as sudden. By univariate analysis, left ventricular ejection fraction, ventricular premature beat frequency, couplet frequency, ventricular tachycardia frequency, functional class, treadmill exercise time and nonischemic heart disease were statistically associated with mortality. With multiple logistic regression analysis, left ventricular ejection fraction was identified as the variable most closely associated with total mortality (p = 0.006). Twenty-seven percent of patients with an ejection fraction less than or equal to 20% died compared with 7% with an ejection fraction greater than or equal to 30%. Ventricular tachycardia frequency on Holter monitoring was independently associated with both total mortality (p = 0.008) and sudden death (p = 0.003). Patients with a ventricular tachycardia frequency of greater than 0.088 events/h had a mortality rate of 34% compared with 12% in those without ventricular tachycardia. In the multivariate model, functional class (p = 0.02) and etiology of nonischemic heart disease (p = 0.04) remained as independent predictors of mortality, whereas treadmill exercise duration did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output, Low↗
PubMed1989

Prognostic importance of atrial natriuretic peptide in patients with chronic heart failure.

Several circulating neurohormones have been shown to have prognostic significance in patients with chronic heart failure, but the relation between plasma levels of atrial natriuretic peptide and mortality in this disorder remains unknown. Plasma levels of immunoreactive atrial natriuretic peptide were measured in 102 patients in whom left ventricular ejection fraction, ventricular arrhythmias on ambulatory electrocardiographic recording and plasma levels of norepinephrine, renin activity, aldosterone and arginine vasopressin were also measured. Compared with patients with atrial natriuretic peptide concentrations below the median value of 125 pg/ml, patients with higher levels of the peptide had a higher plasma renin activity (8.9 +/- 1.8 versus 2.6 +/- 0.4 ng/ml per h) and plasma norepinephrine (858 +/- 116 versus 538 +/- 45 pg/ml), more frequent premature ventricular depolarizations (4,485 +/- 715 versus 2,004 +/- 495/day) and more advanced hemodynamic abnormalities (all p less than 0.05). During the subsequent 13 to 25 months of follow-up, patients with high levels of atrial natriuretic peptide had a significantly lower rate of survival than did those whose initial circulating peptide concentrations were normal or mildly increased (p = 0.01). These data indicate that, in patients with chronic heart failure, plasma atrial natriuretic peptide provides important prognostic information. This may relate to the ability of the hormone to reflect the interplay of several pathophysiologic factors that contribute to mortality in this disease.

Adult↗