Biomedical subjects

M L Kukin

Publications and source records attributed to M L Kukin.

28 records · Page 2Linked to original sources

PubMed1991

Hemodynamic effects of renin inhibition by enalkiren in chronic congestive heart failure.

Previous efforts to block the renin-angiotensin system in patients with chronic congestive heart failure (CHF) have focused on 2 distal sites in the system, the angiotensin-converting enzyme and the angiotensin II receptor. Recent work, however, has led to the development of agents that directly inhibit renin, the proximal step in the cascade. In this study, we investigated the hemodynamic effects of renin inhibition in 9 patients with chronic CHF by using enalkiren, a primate-selective, dipeptide renin inhibitor, which has been previously shown to suppress plasma renin activity and to lower blood pressure in hypertensive patients. The acute intravenous administration of enalkiren (1.0 mg/kg) produced increases in cardiac index (2.0 +/- 0.3 to 2.3 +/- 0.1 liter/min/m2) and stroke volume index (26 +/- 3 to 34 +/- 4 ml/m2) and decreases in left ventricular filling pressure (31 +/- 3 to 25 +/- 3 mm Hg), mean right atrial pressure (15 +/- 1 to 13 +/- 2 mm Hg), heart rate (78 +/- 5 to 72 +/- 6 beats/min) and systemic vascular resistance (2,199 +/- 594 to 1,339 +/- 230 dynes.s.cm-5) (all p less than 0.01 to 0.05). These observations indicate that renin inhibition produces hemodynamic benefits in patients with chronic CHF and could potentially provide a novel approach to interfering with the renin-angiotensin system in patients with this disorder.

Adult↗

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

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↗

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

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↗

PubMed1989

The current status of angiotensin converting enzyme inhibitors in the management of patients with chronic heart failure.

Angiotensin converting enzyme (ACE) inhibitors are the only therapeutic agents used in the treatment of chronic heart failure that have been shown to both improve symptoms and prolong life. These agents produce long-term haemodynamic and clinical benefits in about 60-65% of patients. The only reliable means of determining which patients are most likely to respond favourably to treatment is by a therapeutic trial; the response cannot be predicted by demographic factors, pretreatment left ventricular function or plasma renin activity. In addition to their symptomatic benefits, ACE inhibitors reduce the mortality of patients with chronic heart failure, possibly by decreasing ventricular wall stress and decreasing the frequency and complexity of ventricular arrhythmias. The most serious adverse effects of treatment, hypotension, functional renal insufficiency and potassium retention, occur most commonly in patients with the most advanced disease [New York Heart Association (NYHA) class III and IV heart failure] and when efforts are made to block the formation of angiotensin (Ang) II continuously (as with the use of long-acting ACE inhibitors). The unique characteristics of the ACE inhibitors support their use as first-line agents in patients with chronic heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1987

Role of neurohormonal mechanisms in determining survival in patients with severe chronic heart failure.

Support for the concept that neurohormonal mechanisms play an important role in determining the survival of patients with severe chronic heart failure is derived from two lines of evidence: circulating levels of neurohormones are markedly elevated in patients who have a poor long-term prognosis and the survival of high-risk patients may be favorably modified by treatment with specific neurohormonal antagonists. Plasma norepinephrine is a major prognostic factor in patients with severe chronic heart failure, the most markedly elevated levels being observed in patients with the most unfavorable long-term prognosis. Data from uncontrolled studies suggest that low-dose beta-blockade may improve the survival of patients with dilated cardiomyopathy. Similar trends were noted in the Beta-Blocker Heart Attack Trial, in which patients with congestive heart failure before or accompanying their acute myocardial infarction experienced a significant reduction in sudden death when treated with beta-blockers. In contrast, there appeared to be little selective benefit in patients without heart failure, who presumably had low circulating levels of catecholamines. Similarly, serum sodium concentration is a major prognostic factor in patients with severe chronic heart failure, the shortest survival being observed in patients with the most severe hyponatremia. The poor long-term outcome of hyponatremic patients appears to be related to the marked elevation of plasma renin activity in these individuals, since (in retrospective studies) hyponatremic patients appeared to fare significantly better when treated with converting-enzyme inhibitors than when treated with vasodilator drugs that did not interfere with angiotensin II formation. In contrast, there appeared to be no selective benefit of converting-enzyme inhibition on the survival of patients with a normal serum sodium concentration, in whom plasma renin activity was low. These data suggest that neurohormonal systems may exert a deleterious effect on the survival of some patients with severe chronic heart failure, which may be favorably modified by long-term treatment with specific neurohormonal antagonists.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Are all beta blockers the same for heart failure?

Based on impressive morbidity and mortality data using beta blockers in heart failure, this therapy has now become part of the standard of care for patients with New York Heart Association II/III symptoms. The question remains whether there are clinically relevant differences between the beta blockers that have shown beneficial effects. This review summarizes the major mortality trials, and examines the smaller comparative trials of second and third generation beta blockers.

Journal Article↗

PubMedDate not supplied

Ambulatory ventricular arrhythmias in patients with heart failure do not specifically predict an increased risk of sudden death. PROMISE (Prospective Randomized Milrinone Survival Evaluation) Investigators.

BACKGROUND: Ventricular arrhythmias are a frequent finding in congestive heart failure (CHF) patients and a cause of concern for physicians caring for them. Previous studies have reached conflicting conclusions regarding the importance of ventricular arrhythmias as predictors of sudden death in patients with CHF. This study examined the independent predictive value of ventricular arrhythmias for sudden death and all-cause mortality in PROMISE (Prospective Randomized Milrinone Survival Evaluation). METHODS AND RESULTS: Ventricular arrhythmias were analyzed and quantified by use of prespecified criteria on baseline ambulatory ECGs from 1080 patients with New York Heart Association (NYHA) class III/IV symptoms and a left ventricular ejection fraction </=35% enrolled in PROMISE. The relationship of ventricular arrhythmias and other clinical parameters to overall mortality and sudden death classified by an independent, blinded mortality committee was determined. There were 290 deaths, of which 139 were classified as sudden. Of the several measures of ventricular ectopy that were univariate predictors, the frequency of nonsustained ventricular tachycardia (NSVT) was the most powerful predictor and remained a significant independent predictor when included with other clinical variables in multivariate models of both sudden death mortality and non-sudden death mortality. However, multiple logistic analysis with models including the clinical variables with and without the NSVT variable demonstrated that the frequency of NSVT did not add significant information beyond the clinical variables. CONCLUSIONS: This study demonstrates that ventricular arrhythmias do not specifically predict sudden death in patients with moderate-to-severe heart failure. Thus, the finding of asymptomatic NSVT on ambulatory ECG does not identify specific candidates for antiarrhythmic or device therapy.

Arrhythmias, Cardiac↗

PubMedDate not supplied

Safety and efficacy of beta blockade in patients with chronic congestive heart failure awaiting transplantation.

BACKGROUND: Donor availability remains a limiting factor for heart transplantation while transplant waiting time entails significant morbidity and mortality. This study was designed to assess the efficacy and safety of long-term beta blockade as optimization of therapy in patients with severe congestive heart failure already receiving digoxin, diuretics, and converting enzyme inhibitors awaiting transplantation. METHODS: The beta-1 antagonist metoprolol was given to 19 patients with moderate to severe congestive heart failure. Hemodynamic, clinical, and neurohormonal measurements were obtained before drug therapy and after 3 months of treatment. Patients initially received 6.25 mg of metoprolol orally twice daily which was increased to a target dose of 50 mg twice daily over several weeks. RESULTS: Metoprolol produced significant clinical, exercise, and hemodynamic benefits. Long-term therapy was associated with improvements in New York Heart Association class, ejection fraction, 6-minute walk, and peak maximal oxygen consumption. There were significant decreases in heart rate, pulmonary arterial systolic pressure, and left ventricular filling pressure with significant increases in stroke volume index and stroke work index. Four patients were removed from the transplant list after improving to New York Heart Association I. Only one patient required hospitalization during the first 6 months of therapy. There were no deaths caused by progressive heart failure; however, one patient died suddenly. CONCLUSIONS: Beta blockade with metoprolol can be safely administered to patients awaiting heart transplantation producing clinical, exercise, and hemodynamic improvements. Thus, beta blockade may prove to be a safe and cost-effective bridge to transplantation.

Adrenergic beta-Antagonists↗