Francisco Navarro-Lopez

Determinants of prognosis in survivors of myocardial infarction: a prospective clinical angiographic study.

To identify predictors of late mortality, 259 consecutive men (less than or equal to 60 years old) who survived acute myocardial infarctions were catheterized one month after admission and were then followed for a mean of 34 months. Nineteen patients (7 per cent) died during the observation period. Of 79 base-line descriptors, 17 proved to be univariate predictors of survival. Cox regression analysis demonstrated that the ejection fraction (P less than 0.001), the number of diseased vessels (P less than 0.005), and the occurrence of congestive heart failure in the coronary unit (P less than 0.01) were the only independent predictors of survival. Risk stratification showed that the probability of survival at four years was highest in patients with normal ejection fractions (96 to 100 per cent, depending on the number of diseased vessels) and lowest in those with ejection fractions below 20 per cent (3o to 75 per cent). The prognosis in patients with ejection fractions between 21 and 49 per cent was significantly worse (78 per cent) than in those with normal ejection fractions only in the group with three-vessel involvement (P less than 0.01). Since most survivors of myocardial infarction who are likely to have their lives prolonged by coronary-artery bypass surgery are in this group, it is reasonable to limit routine coronary angiography to the 56 per cent of survivors who have ejection fractions between 21 and 49 per cent.

ENHANCED DETECTION CRITERIA IN IMPLANTABLE DEFIBRILLATORS

Enhanced Tachycardia Detection Algorithm introduction: Enhanced detection criteria in third‐generation implantable defibrillators have been implemented to avoid inappropriate therapy of fast supraventricular arrhythmias. We prospectively analyzed the use of these criteria in patients with an implantable defibrillator with electrogram storing capability.

Myocardial infarction with normal coronary arteries: A prospective clinical-angiographic study

The association of myocardial infarction with normal coronary arteries was analyzed prospectively. A series of 259 consecutive men aged 60 years or less underwent selective coronary angiography 30 days after a definite infarct. Coronary arterial lesions were documented in 251 patients, normal coronary arteries in the remaining 8. The latter patients had a significantly lower (p less than 0.001) mean age than the former; no patient older than 50 years had patent coronary arteries, whereas 5 of the 11 patients under age 35 had normal arteries. The prevalence of risk factors was similar in both groups of patients. Although there were no group differences in infarct size or location, patients with normal coronary arteries had a higher ejection fraction (p less than 0.01) and a lower left ventricular end-diastolic pressure (p less than 0.05). A previous history of angina or infarction and the occurrence of new coronary events were confined to patients with coronary arterial lesions. The clinical course of patients presenting with normal angiograms was uneventful. Transient coronary occlusion, the most likely mechanism of infarction in this group of patients, could not be ascribed to either spasm or platelet hyperactivity.

Comparison of the effects of amiodarone versus metoprolol on the frequency of ventricular arrhythmias and on mortality after acute myocardial infarction

A randomized trial was conducted to assess the efficacy of amiodarone versus metoprolol or no antiarrhythmic treatment to suppress asymptomatic ectopic activity and improve survival in patients who have had myocardial infarction with a left ventricular ejection fraction of 20 to 45% and > or = 3 ventricular premature complexes per hour (pairs or runs). Patients (n = 368) were randomly assigned to receive amiodarone 200 mg/day (n = 115) 10 to 60 days after the acute episode, and metoprolol 100 to 200 mg/day (n = 130) or no antiarrhythmic therapy (n = 123). After a median follow-up of 2.8 years, mortality in the amiodarone-treated patients (3.5 +/- 2% SEM) did not differ significantly from that of untreated control subjects (7.7 +/- 2.5%, p = 0.19), but was lower than that in the metoprolol group (15.4 +/- 3.5%, p = 0.006). Patients treated with metoprolol had twice the mortality seen in control subjects, even though the differences were not statistically significant. Holter studies performed at 1, 6 and 12 months showed that both amiodarone and metoprolol were equally effective in reducing heart rate, whereas only amiodarone significantly reduced ectopic activity (p < 0.0001). Thus, long-term treatment with amiodarone was clearly safe in patients with an ejection fraction of 20 to 45%, was effective in suppressing arrhythmias, and was associated with a lower mortality than metoprolol; corroboration is required in a larger trial.

Isolated T wave alternans

Two patients with isolated T wave alternans are reported, with their vectocardiograms, their response to carotid sinus stimulation, and the response to calcium infusion in one of them with documented severe hypocalcemia. Eleven cases of the literature are briefly reviewed. The alternans of the T wave appears with severe QT prolongation, QT alternans, and an increased tendency to ventricular fibrillation. The findings are consistent with the hypothesis that T wave alternans may be the electrocardiographic manifestation of the transmembrane action potential alternans and could be related in some cases to hypocalcemia.

Cardiomyopathy mutations reveal variable region of myosin converter as major element of cross-bridge compliance.

The ability of myosin to generate motile forces is based on elastic distortion of a structural element of the actomyosin complex (cross-bridge) that allows strain to develop before filament sliding. Addressing the question, which part of the actomyosin complex experiences main elastic distortion, we suggested previously that the converter domain might be the most compliant region of the myosin head domain. Here we test this proposal by studying functional effects of naturally occurring missense mutations in the beta-myosin heavy chain, 723Arg --> Gly (R723G) and 736Ile --> Thr (I736T), in comparison to 719Arg --> Trp (R719W). All three mutations are associated with hypertrophic cardiomyopathy and are located in the converter region of the myosin head domain. We determined several mechanical parameters of single skinned slow fibers isolated from Musculus soleus biopsies of hypertrophic cardiomyopathy patients and healthy controls. Major findings of this study for mutation R723G were i), a >40% increase in fiber stiffness in rigor with a 2.9-fold increase in stiffness per myosin head (S( *)(rigor R723G) = 0.84 pN/nm S( *)(rigor WT) = 0.29 pN/nm); and ii), a significant increase in force per head (F( *)(10 degrees C), 1.99 pN vs. 1.49 pN = 1.3-fold increase; F( *)(20 degrees C), 2.56 pN vs. 1.92 pN = 1.3-fold increase) as well as stiffness per head during isometric steady-state contraction (S( *)(active10 degrees C), 0.52 pN/nm vs. 0.28 pN/nm = 1.9-fold increase). Similar changes were found for mutation R719W (2.6-fold increase in S( *)(rigor); 1.8-fold increase in F( *)(10 degrees C), 1.6-fold in F( *)(20 degrees C); twofold increase in S( *)(active10 degrees C)). Changes in active cross-bridge cycling kinetics could not account for the increase in force and active stiffness. For the above estimates the previously determined fraction of mutated myosin in the biopsies was taken into account. Data for wild-type myosin of slow soleus muscle fibers support previous findings that for the slow myosin isoform S( *) and F( *) are significantly lower than for fast myosin e.g., of rabbit psoas muscle. The data indicate that two mutations, R723G and R719W, are associated with an increase in resistance to elastic distortion of the individual mutated myosin heads whereas mutation I736T has essentially no effect. The data strongly support the notion that major elastic distortion occurs within the converter itself. Apparently, the compliance depends on specific residues, e.g., R719 and R723, presumably located at strategic positions near the long alpha-helix of the light chain binding domain. Because amino acids 719 and 723 are nonconserved residues, cross-bridge stiffness may well be specifically tuned for different myosins.

Disabling angina pectoris with normal coronary arteries in patients undergoing long-term hemodialysis

Reports of patients undergoing long-term hemodialysis presenting with angina pectoris have usually shown severe coronary atherosclerosis. We studied a series of nine patients undergoing regular maintenance dialysis referred for incapacitating angina. Of them, four had strictly normal coronary angiograms. The patients with normal angiograms were all females who were significantly younger (p less than 0.05) and had more severe hypertension and higher left ventricular wall stress than patients showing coronary artery lesions. Anemia and increased myocardial oxygen consumption due to high blood pressure may explain the syndrome of angina pectoris in the presence of long-term dialysis in patients with normal coronary arteries. The prevalence of this association cannot be ascertained unless prospective studies are conducted. However, our data suggest that it might not be an uncommon finding.

Prevalence and prognosis after a first nontransmural myocardial infarction

Prevalence, prognosis, and coronary anatomy associated with nontransmural myocardial infarction (MI) were prospectively assessed in 458 consecutive men admitted to our coronary care unit with a first MI. Cardiac catheterization was performed in 402 of the 436 survivors within 1 month of the acute event. Mean follow-up was 33 months (range 5 to 72). Nontransmural MI was diagnosed in 28 patients (6%). These patients were younger (46 +/- 10 versus 51 +/- 7 years, p less than 0.001) and had lower peak creatine kinase values (601 +/- 319 versus 1,141 +/- 923 U, p less than 0.01) and better ejection fraction (63 +/- 8 versus 46 +/- 14, p less than 0.001) than did their counterparts. Survivors of nontransmural MI also had fewer affected arteries (p less than 0.001) and a lower prevalence of total or subtotal occlusion (greater than 90%) in the involved artery (p less than 0.01). Mortality in the acute phase and long-term survival at 4 years (Kaplan-Meier) in patients with nontransmural MI (94%) were similar to those in patients with transmural MI (90%). The occurrence of new nonfatal coronary events was also similar in both groups of MI survivors. Thus, in the absence of symptoms, more aggressive management to improve survival does not seem warranted after nontransmural MI.

Preventing ventricular dysfunction in pacemaker patients without advanced heart failure: results from a multicentre international randomized trial (PREVENT-HF)

Previous experimental and clinical studies have consistently suggested that right ventricular (RV) apical pacing has important adverse effects. Ventricular pacing (VP), however, is required, and cannot be reduced in many patients with atrioventricular (AV) block. The PREVENT‐HF study was an international randomized trial that explored differences in left ventricular (LV) remodelling during RV apical vs. biventricular (BIV) pacing in patients with AV block.

Atrial fibrillation induced by atrioventricular nodal reentrant tachycardia

In 4 patients with recurrent episodes of paroxysmal atrial fibrillation as the only documented arrhythmia, electrophysiologic study showed that atrial fibrillation originated after a very fast transition from atrioventricular nodal reentrant tachycardia. Recognition of atrioventricular nodal reentrant tachycardia as the triggering factor for atrial fibrillation has important therapeutic consequences.