Heart rate variability as a means of assessing prognosis after acute myocardial infarction: A 3-year follow-up study

AIMS: The present study evaluated the prognostic value of heart ratevariability after acute myocardial infarction in comparisonwith other known risk factors. The cut-off points that maximizedthe hazards ratio were also explored. PATIENTS AND METHODS: Heart rate variability was assessed with 24 h ambulatory electrocardiographyin 74 patients with acute myocardial infarction, 4±2days after hospital admission and in 24 healthy controls. Patientswere followed for 36±15 months. RESULTS: During follow-up, 18 patients died, nine suffered a non-fatalinfarction and 20 underwent revascularization procedures. Heartrate variability was higher in survivors than in non-survivors(P=0·0005) This difference was found at higher statisticallevels when comparing non-survivors vs controls (P=0·0002)A similar statistically significant difference was also foundbetween survivors vs controls (P=0·04). Patients sufferingnon-fatal infarction and cardiac events (defined as death, non-fatalinfarction or revascularization) had a lower heart rate variabilitythan those without (P=0·03 and P=0·03, respectively).With multivariate regression analysis, decreased heart ratevari ability independently predicted mortality and death ornon-fatal infarction. The presence of a left ventricular ejectionfraction <40% and a history of systemic hypertension were,however, stronger predictors. The cut-off points that maximizedthe hazards ratio using the Cox model differed from those reportedby others. CONCLUSIONS: Decreased heart rate variability independently predicted poorprognosis after myocardial infarction. However, the cut-offpoints that should be used in clinical practice are still amatter for further investigation.     

QT interval dispersion as a predictor of arrhythmic events in congestive heart failure: Importance of aetiology

Aims Identification of patients with congestive heart failure atrisk of sudden death remains problematic and few data are availableon the prognostic implications of QT dispersion. We sought toassess the predictive value of QT dispersion for arrhythmicevents in heart failure secondary to dilated cardiomyopathyor ischaemic heart disease. Methods and Results Twelve-lead ECGs calculated for QT dispersion, 24h Holter ECGsand signal-averaged ECGs were prospectively recorded in 205heart failure patients in sinus rhythm. The 86 patients withischaemic heart disease and the 119 with dilated cardiomyopathywere not significantly different as regards NYHA grades (51vs 49% in grades III–IV), cardiothoracic ratio (57±7vs 57±6%) and ejection fraction (28±8 vs 29±9%).The mean QT dispersion (66±29 vs 65±27ms), thefrequency of non-sustained ventricular tachycardia (37 vs 38%)and ventricular late potentials (41 vs 40%) were not significantlydifferent in patients with ischaemic or dilated cardiomyop-athy.QT dispersion was not significantly related to other arrhythmogenicmarkers. During follow-up (24±16 months), 66 patientsdied, 22 of them died suddenly and seven presented a spontaneoussustained ventricular tachycardia. In patients with dilatedcardiomyopathy, in multivariate analysis, only a QT dispersion>80ms was an independent predictor of sudden death (RR: 4·9,95% CI 1·4–16·8,P<0·02) and arrhythmicevents (RR: 4·5, 95% CI 1·5–13·5,P<0·01).In patients with ischaemic heart disease, no studied parameterwas found significantly related to sudden death or arrhythmicevents. Conclusion: In congestive heart failure, abnormal QT dispersion can identifypatients with dilated cardiomyopathy who are at high risk ofarrhythmic events.     

Risk stratification after myocardial infarction: A reappraisal in the era of thrombolysis

Objectives The present study was performed to evaluate whetherthe modalities of risk stratification after myocardial infarctionwere still operative in the thrombolytic era. Background Prediction of fatal events in the aftermath of myocardialinfarction relies on tests which aim to assess myocardial function,residual ischaemia and propensity for ventricular arrhythmias.Recent data on improved myocardial infarction prognosis haveled to the view that risk stratification needs to be updated. Methods In this multicentre, prospective study, 471 acute myocardialinfarction patients, 45% of whom were given thrombolytic therapy,were enrolled from the 10th day and underwent all or part ofthe following tests: exercise test, radionuclide ventriculography(resting and exertional ejection fraction), Holter monitoring,signal-averaged electrocardiography and programmed electricalstimulation. Univariate and multivariate analyses were performedto identify predictors of mortality. Results One year and long-term (mean follow-up 31·4 months)mortality rates were 5·5% and 8·4% respectively.Prediction of mortality was assessed and the role of the followingvariables was thus determined: age over 56 years (P=0·01),previous coronary attacks (P>0·001), history of heartfailure (P>0·001), early heart failure after myocardialinfarction (P=0·017), maximum workload of lest than 120W at exercise test (P=0·014), ineligibility to performexercise (P=0·002), depressed left ventricular ejectionfraction (P=0·013), late potentials as identified using50 Hz high pass filtering (P=0·012), mean night-timecycle length of less than 750 ms (P0·001), standard deviationof day time RR intervals of less than 100 ms (P=0·04),the last two measures reflecting heart rate variability. Inthis population, neither ventricular ectopic activity nor inducibilityof sustained monomorphic ventricular tachycardia at electrophysiologicalstudy carried any prognostic significance. Multivariate analysesshowed that decreased heart rate variability, presence of latepotentials and low ejection fraction (>30%) made an independentcontribution to the survival models. Conclusion In the current context of management of acute coronarypatients, the basis for risk stratification after myocardialinfarction remain roughly unchanged.     

Long-term outcome of patients with incomplete vs complete revascularization after multivessel PTCA: A report from the NHLBI PTCA Registry

Background Incomplete revascularization is frequently the goalas well as the final outcome in patients with multivessel coronarydisease undergoing PTCA. However, the long-term impact of incompleterevascularization is not known and this common PTCA strategydeserves further scrutiny. Methods and results Complete revascularization was achievedin 132 of 757 patients with multivessel disease in the 1985–86NHLBI PTCA Registry. Compared to patients in whom complete revascularizationwas achieved, patients with incomplete revascularization wereolder (P<0·05), more likely to be females (P<0·05)and to have recent myocardial infarction (P<0·05),unstable angina (P<0·001), and urgent or emergentPTCA (P<0·001). Early death, Q wave myocardial infarctionand CABG rates were higher in patients with incomplete thanin those with complete revascularization [significantly different(P<0·05) only for emergency and elective CABG]. At9 years, nearly twice as many patients with incomplete revascularizationexperienced recurrent angina (19% vs 10% for patients with completerevascularization,P<0·05). Patients with completerevascularization were more likely to undergo repeat PTCA thanthose with incomplete revascularization (40% vs 30%,P<0·05).Patients with incomplete revascularization were more likelyto undergo CABG than patients with complete revascularization(32% vs 14%,P<0·001; adjusted risk 2·56, 95%CI 1·60, 4·10). Among patients with incompleterevascularization, those in whom PTCA was intended but not attemptedhad the highest early event rates and late CABG rates. Finally,the adjusted risk of dying, having a Q wave myocardial infarction,recurrent angina or repeat PTCA was not different at 9-yearfollow-up among patients with and without complete revascularization. Conclusions Complete revascularization achieved by PTCA reduceslate occurrence of CABG, but not adjusted rates of death, Qwave myocardial infarction, recurrent angina, and repeat PTCAin patients with multivessel coronary disease. These data tendto support the PTCA strategy of incomplete revascularizationin patients with multivessel disease when complete revascularizationis not feasible or not planned before the procedure.     

Two-year time course and significance of neurohumoral activation in the Survival and Ventricular Enlargement (SAVE) Study

Aims To describe the temporal evolution of neurohumoral activationin survivors of myocardial infarction with left ventriculardysfunction who are initially asymptomatic and to relate thisto prognosis. Methods and Results Patients in the neurohumoral substudy (n=534)of the Survival and Ventricular Enlargement (SAVE) study hadtheir neurohormones measured at baseline, 3, 12 and 24 monthspost-infarction, were followed 38±7 months and had thesevalues related to prognosis. All patients had a left ventricularejection fraction 40% early post-infarction. Atrial natriureticpeptide, aldosterone, norepinephrine and plasma renin activitydecreased progressively over time. Patients with events hada persistent increase in these neurohormones with those dyingwithin the first 24 months of follow-up having the greatestincrease. Treatment with captopril affected only plasma reninactivity (increase) and aldosterone (decrease). For patientswho remained asymptomatic for the first 3 months post-infarction(n=471), by multivariate analyses (all neurohormones togetherwith non-neurohumoral risk factors), 3-month plasma atrial natriureticpeptide and aldosterone were the most closely related to thedevelopment of severe heart failure or to the combined end-points(cardiovascular death, myocardial infarction, or severe heartfailure). No neurohormone was related to recurrent myocardialinfarction or to cardiovascular mortality. When the last neurohormonemeasured prior to an event was considered along with non-neurohumoralrisk factors (adjusted univariate), atrial natriuretic peptide,aldosterone, norepinephrine and epinephrine were associatedwith prognosis indicating that a time-dependent analysis identifieda closer relationship between neurohormones and events thanthat identified by 3-month values. However, by multivariateanalyses atrial natriuretic peptide was the only neurohormoneassociated with an event, being associated with the developmentof severe heart failure (P<0·001) and the combinedend-points (P=0·022). However, when neurohormones werecon-sidered as binary variables, activated or non-activated(defined as >1·96SD above the mean of age-matched controls),an association between activation of norepinephrine prior torecurrent myocardial infarction (P<0·001) and combinedend-points (P<0·01) and between activation of aldosteroneand severe heart failure (P<0·05) was identified. Conclusions Neurohumoral activation decreases pro-gressivelypost-infarction, but only in patients with a good prognosis.In patients with a left ventricular ejection fraction 40% andasymptomatic post-infarction plasma atrial natriuretic peptideat 3 months, aldosterone levels appeared to be the neurohormonesmost closely associated with prognosis. Increased levels ofatrial natriuretic peptide, aldosterone and norepinephrine appearto be temporally most closely associated with events.     

Changes in platelet size and count in unstable angina compared to stable angina or non-cardiac chest pain

Aims An increase in platelet aggregability is associated withunstable angina and myocardial infarction. Platelet size andactivity correlate and mean platelet volume was found to beincreased before acute myocardial infarction. We measured themean platelet volume and platelet count in patients with stableangina, unstable angina and non-cardiac chest pain. Methods and results We studied 981 patients (734 men; 247 women)defined clinically as stable angina (n=688), unstable angina(n=108) and unstable angina requiring immediate angioplasty(n=52). After coronary angiography the patients were subdividedinto single (n=269), double (n=304) and triple-vessel disease(n=311) and the control group of non-cardiac chest pain (n=97).There was no significant difference in platelet count betweenthe control group and patients with 1, 2, or 3-vessel disease.However, the platelet size in patients with coronary arterydisease was significantly larger (single: 8·7±1·19fl;double: 8·7±1·12fl; triple-vessel disease:8·8±1·18fl) than the control group (8·2±0·95fl)(P<0·01). Patients with stable angina similarly hadno significant difference in platelet count compared to thecontrol group but did have a significantly increased mean plateletvolume (8·7±1·13;P<0·01). Incontrast, patients with unstable angina had a decreased plateletcount (245±56x10/l) compared to either stable angina(262±62x10/l;P<0·05) or the control group (261±58x10/l;P<0·05);furthermore, the mean platelet volume (9·4±1·23fl)was significantly greater than for stable angina (P<0·01).Patients with unstable angina requiring immediate PTCA had aneven lower platelet count (231±55x10/l) and higher meanplatelet volume (10·4±1·03fl) (P<0·01)than the rest of the population with unstable angina. Conclusions In stable angina the platelet count is unchangedcompared to patients with normal coronary arteries but the plateletsize is increased. However, in unstable angina there is a decreasein platelet count and an even larger increase in platelet size.We interpret this as meaning that unstable angina might be associatedor preceded by an increase in platelet destruction rate thatis not completely compensated for by an increase in plateletproduction rate. The large, more reactive platelets might becausally related to an ongoing coronary artery obstruction inunstable angina.     

Comparison of two methods of determining renal perfusion with and without captopril pretreatment in groups of patients with left ventricular dysfunction

Methods of effective renal plasma flow measurement by ¹²⁵I-orthoiodohippurateelimination and para-aminohippurate clearance were comparedwith and without captopril pretreatment in 10 chronic heartfailure patients and in 20 patients after transmural myocardialinfarction. In the chronic heart failure group measurements of effectiverenal plasma flow by the two techniques were strongly correlated(r=0·92, P<0·00001), as was the captopril-mediatedchange in effective renal plasma flow by the two methods (r=0·85,P=0·002). However, in absolute terms para-aminohippurateclearance significantly exceeded ¹²⁵I-orthoiodohippurate clearanceby a mean (± SD) of 24·8 ± 43·7ml. min^–1 (P<0·05) so that only using the formertechnique was a signifincant in renal perfusion observed inresponse to converting enzyme inhibition. In the post-myocardial infarction group, correlations betweenthe two methods were variable and much poorer than in the chronicheart failure group (r=0·54, P=0·01 and r=0·74,P=0·002 on consecutive days). Furthermore, captoprilmediatedincrements in effective renal plasma flow by the two techniqueswere unrelated (r= – 0·19, P=0·59). In thisgroup ¹²⁵I-orthoiodohippurate elimination significantly exceededpara-aminohippurate clearance (P<0·05). This reversedassociation and the weaker relationships between methods inpost-infarction as compared to chronic heart failure patientsmay be related to interference by thrombolytic or aspirin treatments.     

Sympathetic predominance of cardiac autonomic regulation in patients with left free wall accessory pathway and orthodromic atrioventricular reentrant tachycardia

AIMS: The aim of this study was to compare cardiac autonomic regulationin patients with a history of paroxysmal supraventricular tachyarrhythmias,such as atrioventricular nodal reentrant tachycardia and atrioventricularreentrant tachycardia, and healthy controls. METHODS AND RESULTS: Seventeen patients with paroxysmal atrioventricular nodal reentranttachycardia (atrioventricular nodal reentrant tachycardia group),14 patients with overt preexcitation and paroxysmal atrioventricularreentrant tachycardia caused by a left free wall accessory pathway(atrioventricular reentrant tachycardia group) and 14 healthycontrol subjects, were studied. The patients and the controlswere age and gender matched. Cardiac autonomic regulation wasassessed by means of frequency domain analysis of heart ratevariability at rest, during head-up tilt, active standing, treadmillexercise and after exercise. The high frequency component (0·15–0·5 Hz)of heart rate variability tended to be lower and the low frequencycomponent (0·04–0·15 Hz) tended to be higheramong the atrioventricular reentrant tachycardia patients thanin atrioventricular nodal reentrant tachycardia patients andcontrols. The difference reached statistical significance atrest (P<0·05) and during standing (P<0·05atrioventricular reentrant tachycardia vs atrioventricular nodalreentrant tachycardia and P<0·01 atrioventricularreentrant tachycardia vs controls). Accordingly, the low-to-highfrequency ratio — the marker of cardiac sympathetic regulation— was higher in atrioventricular reentrant tachycardiapatients than in atrioventricular nodal reentrant tachycardiapatients (P<0·05 at rest and during standing) andcontrols (P<0·01 during standing). CONCLUSION: The cardiac autonomic status in atrioventricular reentrant tachycardiapatients was suggestive of a higher sympathetic tone than inatrioventricular nodal reentrant tachycardia patients or healthycontrols. This may be related to inhomogeneous ventricular activationin the presence of antegrade conduction via the accessory atrioventricularpathway.     

High intensity knee extensor training, in patients with chronic heart failure: Major skeletal muscle improvement

Skeletal muscle adaptations to high intensity knee extensorstrength and/or endurance training in patients with chronicheart failure were investigated. Eleven patients with chronicheart failure were randomized into two groups and exercisedthe m. quadriceps femoris 3 days/week for 8 weeks. After training,the maximal exercise intensity tolerated on the ergometer cyclewas raised from 99 (32) to 114 (40) watts (W, P<0·05)for all 11 patients. Peak dynamic knee extensor work rate showedthe greatest increase after endurance training (40%, P<0·01).Maximal dynamic and isometric strength were elevated by 40–45%(P<0·05) after strength training. The cross-sectionalarea of m. quadriceps femoris was increased in the strength-trainedlegs (9%, P<0·05), and the capillary per fibre ratioof m. vastus lateralis was raised by 47 and 58% in the endurance-trainedlegs (P<0·05). The oxidative enzyme activity in m.vastus lateralis was significantly raised above 50% after endurancetraining, whereas glycolytic enzyme activity was unaltered.The peripheral skeletal musculature in patients with chronicheart failure adapts fairly quickly to high intensity knee extensortraining. This results in a marked rise in local, and a smallrise in total work capacity, indicating maintained plasticityof skeletal muscle in chronic heart failure patients.     

Heart rate variability and heart rate in healthy volunteers. Is the female autonomic nervous system cardioprotective?

Aims Heart rate variability has been proposed as an indicator ofcardiovascular health. Since women have a lower cardiovascularrisk, we hypothesized that there are gender differences in autonomicmodulation. Methods and Results In 276 healthy subjects (135 women, 141 men) between 18 and71 years of age, 24h heart rate and heart rate variability weredetermined. All heart rate variability parameters, except forpNN50 and high frequency power, were higher in men. After adjustmentfor heart rate, we obtained gender differences for: the standarddeviation (P=0·049), the standard deviation of the 5minaverage (P=0·047), low frequency power (absolute values,P=0·002;normalized units,P<0·001) and ratio low frequency/highfrequency (P<0·001). There were no significant genderdifferences in heart rate variability parameters denoting vagalmodulation. Gender differences were confined to age categoriesof less than 40 years of age. The majority of heart rate variabilityparameters decreased with age. Only in men, was a higher bodymass index associated with a higher heart rate and with lowerheart rate variability parameters (P<0·001). Conclusion Cardiac autonomic modulation as determined by heart rate variability,is significantly lower in healthy women compared to healthymen. We hypothesize that this apparently paradoxical findingmay be explained by lower sympathetic activity (low frequencypower) in women. This may provide protection against arrhythmiasand against the development of coronary heart disease.     

The influence of muscle mass, strength, fatigability and blood flow on exercise capacity in cachectic and non-cachectic patients with chronic heart failure

BACKGROUND: The influence of age, skeletal muscle function and peripheralblood flow on exercise capacity in chronic heart failure patientsis controversial, possibly due to variations in skeletal muscleatrophy. METHODS AND RESULTS: To assess predictors of exercise capacity in patients with clinicalcardiac cachexia, we studied 16 cachectic and 39 non-cachecticmale chronic heart failure patients of similar age and ejectionfraction. All cachectic patients were wasted (% ideal body weight:81 1·9 vs 105·2±2·1, P<0·mean±SEM) and had documented weight loss (5–30kg). Peak oxygen consumption (14·9±1·4vs 16·3±0·6 ml.kg^–1, min ^–1,resting, and peak blood flow (plethysmography) and 20 min fatigability(% baseline strength) were all similar between the two groups.Quadriceps strength, muscle size (all P<0·0001), strengthper unit muscle (right: P<0·05; left: P<0·0·01)and 5 min fatigability (P<0·05) were all lower incachectic patients. In non-cachectic patients, age (R=0·48and quadriceps strength (R=0·43, all P<0·01)predicted peak oxygen consumption. Only in cachectic patientsdid peak blood flow predict peak oxygen consumption significantly(R=0·72, P0·005), whereas age and strength didnot. Similar findings were confirmed using other previouslypublished definitions of cardiac cachexia. CONCLUSION: The predictors of exercise capacity change with the developmentof cardiac cachexia from age and strength to peak blood flow.This shift may be caused by additional endocrine or catabolicabnormalities active in end stage heart failure.     

Impact of restenosis 10 years after coronary angioplasty

Aims The aim of the study was to compare the 10-year follow-up resultsof patients with or without restenosis following single-vesselpercutaneous transluminal coronary angioplasty (PTCA). Methods and Results A total of 313 patients with successful PTCA (20% reductionin luminal diameter narrowingwithout acute complications) anda control angiography 6 months after PTCA were included in thestudy. Events during the follow-up period were defined as death,myocardial infarction, bypass surgery, or repeat PTCA. Statisticalevaluation was performed by the Fisher test, logistic regression,and life-table analysis. Restenosis (loss of >50% of the initialgain and diameter stenosis of <50%) was found in 87 (28%)patients. During follow-up, 11 patients (5%) without restenosis(group A) and 11 (13%) patients with restenosis (group B) died(P<0·05). In group A, 17 (8%) patients and in groupB, 11 (13%) patients suffered myocardial infarction (ns); 17group A (8%) patients and 25 (29%) group B patients had bypasssurgery (P<0·0001), and 34 (15%) group A patientsand 55 (63%) group B patients underwent repeat PTCA (P<0·0001).Logistic regression analysis identified restenosis as an independentrisk factor that increases the risk of death 2·8-fold(P=0·02), bypass surgery 5·6-fold (P<0·0001),and repeat PTCA 10-fold (P<0·0001). Conclusion: We conclude that patients with restenosis had a poorer long-termoutcome than patients without restenosis. Although most patientswith restenosis underwent repeat PTCA, the survival rate withoutany serious adverse events was only 59%, compared with 83% inpatients without restenosis (P<0·0001).     

Non-invasive assessment of inspiratory muscle performance during exercise in patients with chronic heart failure

Aims The aim of this study was to assess inspiratory performanceat rest and during exercise in patients with chronic heart failurein comparison with healthy controls using a non-invasive index:the tension-time index of inspiratory muscles (TTMUS). Methods We studied 13 patients with chronic heart failure (57±7years) and 10 control subjects (58±6 years) at rest andduring an incremental maximal exercise test. Measurements includedbreathing pattern (inspiratory time, total time of respiratorycycle, minute ventilation, tidal volume and respiratory frequency),mouth occlusion pressure and mean inspiratory pressure (calculatedas follows: 5xmouth occlusion pressurexinspiratory time). Themaximal inspiratory pressure was measured at rest. TTMUS wascalculated from the equation: TTMUS=PI/PIMAXxTI/TTOT, wherePI/PIMAX is the ratio of mean inspiratory pressure to maximalinspiratory pressure and TI/TTOT is the ratio of mean inspiratorytime to total time of the respiratory cycle. Results At rest, the results in patients showed non-significantly highermouth occlusion pressure, lower maximal inspiratory pressure(PP<0·001), and a higher ratio of mean inspiratorypressure to maximal inspiratory pressure (PP<0·01).There was no difference in the breathing pattern. TTMUS wasthus significantly higher in the patients with chronic heartfailure (PP<0·001). At maximal exercise (77±16Wfor patients with chronic heart failure vs 142±27W forcontrols,PP<0·001), the ratio of mean inspiratorytime to total time of respiratory cycle, the mouth occlusionpressure and the ratio of mean inspiratory pressure to maximalinspiratory pressure were not different. TTMUS was thus comparablein the two groups. During exercise, at comparable workloads(20, 40 and 60W), the patients showed higher mouth occlusionpressure (PP<0·01) and a higher ratio of mean inspiratorypressure to maximal inspiratory pressure (PP<0·001),whereas the ratio of mean inspiratory time to total time ofthe respiratory cycle was similar. TTMUS was thus higher inthe patients at each workload (PP<0·05). Conclusion This study shows that the determination of TTMUS at rest andduring exercise allows the observation of alterations in inspiratorymuscle performance as a result of both reduced inspiratory strength,as measured by the maximal inspiratory pressure, and increasedventilatory drive, as reflected by the mouth occlusion pressurein patients with chronic heart failure. The non-invasivenessof this new index is an additional argument for its use in aclinical setting.     

Does in-hospital ventricular fibrillation affect prognosis after myocardial infarction?

AIM: The aim of this study was to estimate the prognostic informationto be gained from ventricular fibrillation in patients withmyocardial infarction. METHODS AND RESULTS: We studied 4259 consecutive patients with myocardial infarctionadmitted to one centre in 1977–1988. Five hundred andtwenty-eight (12·4%) of the patients had ventricularfibrillation in hospital. The following risk factors were includedin multivariate models to estimate their importance for 30-dayand long-term (median 7 year) prognosis: age, gender, ventricularfibrillation, congestive heart failure, pulmonary oedema, cardiogenicshock, other cardiac arrest and atrial fibrillation. We foundthat the odds ratio for death on days 6–30 was 6·34(3·55–11·30, 95% confidence limits, P<0·001)for patients with primary ventricular fibrillation (withoutheart failure) and 4·06 (2·68–6·14,p<0·001) for patients with ventricular fibrillationsecondary to heart failure compared to patients without ventricularfibrillation. For patients surviving more than 30 days, relativerisk of death in those with ventricular fibrillation was 1·11(95% confidence interval 0·93–1·34, P=0·26).Logistic regression analysis of relative risk associated withventricular fibrillation in time intervals, indicated that theimportance of ventricular fibrillation for risk of death wasexhausted during the initial 60 days after infarction. CONCLUSION: Ventricular fibrillation is associated with an independent increasedrisk of death within 0–60 days after infarction. Afterthis period, the prognosis in survivors of ventricular fibrillationdoes not differ significantly from patients without ventricularfibrillation.     

Growth hormone and heart performance: A novel mechanism of cardiac wall stress regulation in humans

OBJECTIVES: This study was designed to assess systolic wall stress and ventricularfunction in patients with deranged growth hormone secretion,in an attempt to elucidate the mechanisms of growth hormoneinteraction with heart performance. DESIGN: A case-control study. SUBJECTS: Thirty patients with active acromegaly, free of diabetes mellitusand coronary artery disease, and 25 subjects with congenitalgrowth hormone deficiency were studied. Twelve growth hormone-deficientsubjects were reevaluated after 12 months of recombinant humangrowth hormone therapy. Two groups of 30 normal subjects eachwere used as controls for the acromegalic and growth hormone-deficientpatients, respectively. RESULTS: In the acromegalics, end-systolic wall stress was reduced (–20%;P<0·01) due to ventricular wall thickening (+26%;P<0·001), whereas cardiac output was significantlyincreased (+20%; P<0·01). The velocity of fibre shorteningwas unchanged. In growth hormone-deficient subjects, end-systolicwall stress was markedly increased (+38%; P<0·001)due to a significant reduction of ventricular wall thickness(–28%; P<0·001), whereas cardiac output wassignificantly decreased (–44%; P<0·001) Replacementtherapy with recombinant human growth hormone produced a partialcorrection of wall thickness and stress. Consequently, systolicperformance and cardiac output improved significantly. CONCLUSION: This study demonstrates that growth hormone plays a role inthe control of cardiac wall stress and performance through amechanism mediated by the effect of growth hormone on myocardialtissue growth. The data may have therapeutic implications incardiac diseases that lead to heart failure.     

Effects of captopril on ventricular arrhythmias in the early and late phase of suspected acute myocardial infarction: Randomized, placebo-controlled substudy of ISIS-4

The antiarrhythmic effect of oral captopril was studied duringthe early (day 3) and late (day 14) phase of acute myocardialinfarction among 304 patients in a randomized placebo-controlledsubstudy of ISIS-4. Ventricular arrhythmias (ventricular ectopic beats per hour)occurred significantly less frequently among captopril-allocatedpatients than among those allocated placebo at day 3 (logarithmicscale: 0·48 ± 0·8 captopril vs 0·84± 1·3 placebo; P<0·003) and at day 14(0·51 ± 1·0 vs 0·77 ± 1·3;P<0·05). The number of patients with frequent ventriculararrhythmias (more than 10 ventricular ectopic beats per hour)was also significantly lower among those allocated captoprilat day 3 (7·3% vs 14·4% P<0·05) andat day 14 (7·3% vs 14·8%; P<0·05). These results support the hypothesis that the activation ofthe renin-angiotensin-aldosterone and sympathetic system mayunderlie heart rhythm disturbances in acute myocardial infarction,and that early use of converting enzyme inhibitor therapy mayameliorate these disturbances. (Eur Heart J 1996; 17: 1506–1510)     

The 60 Minutes Myocardial Infarction Project. Characteristics on admission and clinical outcome in patients with reinfarction compared to patients with a first infarction

Purpose The purpose of the study was to evaluate parameters that characterizepatients with myocardial reinfarction as compared to patientswith a first infarction in clinical practice, and possibly todetermine their clinical outcome. Methods The 60 Minutes Myocardial Infarction Project is a German multicentreprospective observational study in which 136 hospitals are participating.Fourteen thousand, nine hundred and eighty consecutive patientswith acute Q wave myocardial infarction were included from July1992 to September 1994. Results Out of these 14980 patients, there were 2854 (19%) with reinfarctionand 12126 (81%) with a first infarction. Patients with a reinfarctionarrived at the hospital 24min earlier than patients with a firstinfarction (pre-hospital delay 156 vs 180min;P<0·001);the door-to-needle time with reinfarction was longer (38 vs30min;P<0·001); however, patients with reinfarctionwere older (69 vs 66 years;P<0·001), had a lower rateof a diagnostic first ECG (54 vs 71%;P<0·001) andreceived thrombolytic therapy less frequently than patientswith a first infarction (46 vs 52%;P<0·001). A lownumber of patients received primary PTCA (n=205) since onlya few hospitals offered a primary PTCA service at the time thestudy was performed. In patients with reinfarction, there weremore reasons as to why thrombolytic therapy was not given (24vs 21%;P<0·001). Left bundle branch block occurredmore frequently in patients with reinfarction (15 vs 8%;P<0·001).The intra-hospital course in patients with reinfarction wasassociated with an increase of complications and intra-hospitaldeath (23 vs 15%;P<0·001). Conclusions Although reinfarction patients arrived earlier at hospital thanpatients with a first infarction, the former received thrombolytictherapy less frequently than the latter. Patients with reinfarctionwere older, more frequently had a non-diagnostic ECG on admissionand had a higher rate of contraindications against thrombolytictherapy.     

Randomized placebo-controlled study of the effects of simvastatin on haemostatic variables, lipoproteins and free fatty acids

The Oxford Cholesterol Study is a randomized placebo-controlledtrial designed primarily to assess the effects of simvastatinon blood cholesterol levels and side-effects in preparationfor a large, long-term trial of the effects of cholesterol-loweringdrug therapy on mortality. At present there is only limitedevidence from randomized comparisons of the effects of HMG-CoAreductase inhibitors, such as simvastatin, on thrombogenic,as distinct from atherogenic, pathways in coronary heart disease.The present sub-study was carried out to assess the effectsof simvastatin on a range of haemostatic variables, as wellas on free fatty acids and on lipoprotein fractions not studiedin detail previously. At an average of about 2 years after starting study treatment,non-fasting blood samples were obtained from a sequential sampleof 162 participants who had been randomly allocated to receive40 mg (54 patients) or 20 mg (57 patients) daily simvastatinor matching placebo treatment (51 patients). Only patients whoreported taking their study treatment and who were not knownto be diabetic or to be taking some other lipid lowering treatmentwere to be included. The principal comparisons were to be ofthose allocated simvastatin (i.e. 20 and 40 mg doses combined)vs those allocated placebo. Among patients allocated simvastatin, marginally significantlower factor VII antigen levels (12·10%±6·08of standard; 2P<0·05) and non-significantly lowerfactor VII coagulant activity (8·24%±4·99of standard) and fibrinogen concentrations (0·10±0·08g.l^–1) were observed. In contrast, plasminogen activatorinhibitor activity was significantly higher (2·62±1·03IU; 2P<0·01) among patients allocated simvastatin.No significant differences were seen in the other haemostaticfactors studied (e.g. prothrombin fragment 1·2, factorXII and C$$$ inhibitor). Total free fatty acid concentrationwas marginally significantly reduced (2P=0·02) with simvastatin,but none of the reductions in individual free fatty acids wassignificant. Lipoprotein fractions were only measured amongpatients allocated 40 mg daily simvastatin or placebo. Comparedwith placebo, simvastatin produced significant decreases notonly in LDL cholesterol (1·74±0·15 mmol.1^–1;2P<0·0001) but also in VLDL cholesterol (0·28±0·08mmol.1^–1; 2P<0·001) and IDL cholesterol (0·17±0·03mmol.1^–1; 2P<0·0001). There were also lowertriglyceride levels associated with LDL (0·07±0·01mmol.1^–1; 2P<0·0001), IDL (0·03±0·01mmol.1^–1; 2P<0·01) and VLDL (0·27±0·14;2P=0·05). The effects of simvastatin on haemostatic variables appear tobe far less marked than its lipid effects. Given the associationsof haemostatic factors with coronary heart disease incidence,larger randomized comparisons of the HMG-CoA re1ductase inhibitors(and of the newer fibrates, which may produce greater effects)are needed to provide more reliable estimates of the extentto which they influence these variables.     

Eligibility for reperfusion therapy and outcome in elderly patients with acute myocardial infarction

Reperfusion therapy by thrombolysis or angioplasty was consideredin 260 unselected patients consecutively admitted within 6 hof the onset of Q wave myocardial infarction. Rates of reperfusionand in-hospital mortality were compared in 206 patients <70years and 54 patients 70 years. Early reperfusion was obtainedin 864% of the patients under 70 years and in 72·2% ofthose over 70 (P<0·01). Thrombolysis was more frequentlyused in the younger group (66·0% vs 31·5%, P<10^–5and primary angioplasty in the older (44·4% vs 29·6%,P<0·05). Overall in-hospital mortality was higherin the older group (22·2% vs 4·4 P<10^–5After successful reperfusion, mortality was 12·8% inthe patients over 70 and 3·9% in those under 70. Afterfailed or unproven reperfusion, mortality was 46·7% inthe patients over 70 and 7·1% in those under 70. Reperfusiontherapy is feasible in the majority of patients over 70 years,but failure to attempt or to achieve reperfusion is associatedwith a poor outcome. Although not controlled, this study providesan incentive for attempting early reperfusion therapy as oftenas possible in the elderly with acute myocardial infarction.     

Effects of simvastatin on plasma lipid, lipoprotein and apolipoprotein concentrations in hypercholesterolaemia

The effect of 24 weeks of treatment with simvastatin, a newHMG coenzyme A reductase inhibitor (dosages of 20 and40 mg day^–1)on serum lipid, lipoprotein and apolipoprotein A-I and B concentrationsas well as safety parameters and subjective side effects werestudied in 11 patients with familial (FH) and 10 patients withpolygenic hypercholesterolaemia (P-HC). The effects on plasmalipoprotein and apolipoprotein concentrations had already beenachieved after four weeks in both groups and then remained duringthe study. In FH, mean fasting plasma total cholesterol concentrationdecreased from 10·51 to 6·71 mmol l^–1 (36%),and in P-HC from 6·55 to 4·54 mmol l^–1 (31%)at 24 weeks (P<0·001). Mean plasma low density lipoprotein(LDL) cholesterol concentrations also decreased, in FH from8·87 to 5·05 mmol l^–1 (43%) and in P-HCfrom 4–97 to 3–12 mmol l^–1 (37%) at 24 weeks(P<0·001). Furthermore, apolipoprotein B concentrationsdecreased significantly from 2·21 to 1·57 g l^–1(29%)(P<0·001) in FH and from 1·53 to 1·09g l^–1 (29%) (P<0·01) in P-HC. Plasma high densitylipoprotein (HDL) cholesterol increased in both FH and P-HCduring treatment. Increases were seen in both the subfractionsHDL₂ and HDL₃. Simvastatin was well tolerated. No serious clinicalor laboratory adverse effects were observed. It is concludedthat 24 weeks of treatment with simvastatin in doses up to 40mg day^–1 effectively reduces plasma total and LDL cholesterolconcentrations without causing subjective or significant objectiveside effects. Thus, simvastatin may be of great interest infuture studies for prevention of coronary heart disease dueto hypercholesterolaemia.