Abstract: In order to establish normal limits for mean 24 h heart rate ( H R ¯ t and pauses, 24 h ambulatory ECG recordings from 260 healthy subjects 40–79 years of age were analysed. The H R ¯ 24h varied from 53 to 95 beats/min (mean±2 s.d.: 74±I8 beats/min). The minimal H R ¯ t varied from 36 to 78 beats/min (mean± 2 s.d.: 56 ±16 beats/min). Analysis of variance showed an additive effect of smoking, sex, leisure-time physical activity and age on both H R ¯ t, and the effect of the three first factors was statistical significant at the 1% level for both heart rate variables. The males, the non-smokers and the physically active subjects had a lower H R ¯ 24h and a lower minimal H R ¯ t than females, smokers and passive subjects. Older subjects had a lower H R ¯ t was non-significant. A total of 77 subjects (30%) had a pause (R-R interval≥1500 ms), but in only 12 (5%) did the pause exceed 1750 ms with the longest pause measuring 2040 ms. Further analysis of the longest pause in each of the 77 subjects with pauses showed that 46 of the longest pauses occurred at night following a gradual decrease in the R-R intervals for a few beats (‘post-acceleration pauses’). In 12 subjects the longest pause was caused by sinus arrest, and in nine cases a blocked atrial premature beat was thought to be present. Wenckebach A- V block was seen in only two subjects. It is concluded that sex, age, smoking and leisure-time physical activity are all factors that have to be considered for a thorough evaluation of heart rate variables in the 24 h ambulatory ECG.

Abstract: In a prospective serial study of 96 patients with acute myocardial infarction, two dimensional echocardiography identified left ventricular thrombus in 18 patients. The majority of thrombi (15) developed within the first 4 days after admission. In three patients thrombi were identified for the first time 4 months after the acute episode. All 18 patients had received therapeutic anticoagulants on admission and had large anterior wall infarctions complicated by severe pump failure and motion abnormalities echocardiographically. None of the patients had systemic embolisation during the study period. Thus, left ventricular thrombus is a not uncommon though silent complication of acute anterior wall infarction even when patients receive therapeutic anticoagulants.

Abstract: Twenty-six consecutive patients (14 males, 12 females--mean age 66.6) were admitted to an intensive care unit (ICU) because of a rapid ventricular response to atrial fibrillation (RAF). Fourteen of them had been unsuccessfully treated by drugs (other than amiodarone) and/or DC shock before admission. A loading dose of i.v. amiodarone was administered (repeated boluses of 3 mg/kg in 3 min, or 30 min-infusions of 5 to 7.5 mg/kg), followed by continuous infusion, in order to reach a maximal total dosage of 1500 mg in 24 h. This treatment was considered efficacious if a reversion to stable sinus rhythm (SSR) occurred within 24 h and was maintained for more than 48 h. This was achieved in 21 out of 26 patients (80.8%). The mean time between the administration of therapy and the occurrence of SSR was 171 min. The total dose of amiodarone delivered to effect SSR was 6.9 +/- 2.3 mg/kg. No adverse reactions were encountered during the bolus injection but we recommend that continuous infusion be carried out through a central venous catheter to avoid phlebitis. The administration of 7 mg/kg of intravenous amiodarone delivered in 30 min proved a safe and successful first choice of management in atrial fibrillation with a rapid ventricular response.

Abstract: Since 1960, at the National Institutes of Health, ventricular septal myotomy and myectomy has been the mode of treatment for severely symptomatic patients with hypertrophic cardiomyopathy and obstruction to left ventricular outflow who do not respond to medical therapy. Our long-term results of operation for hypertrophic cardiomyopathy are reviewed in 240 patients operated upon prior to 1980. Postoperatively, most patients had improved symptomatically (i.e. 70%) and manifested marked reduction or abolition of the basal left ventricular outflow gradient (i.e. 98%). However, 8% of the patients died of causes related to operation, 9% had persistent or recurrent severe functional limitation, and 7% died up to 19 years postoperatively due to the underlying cardiomyopathy. Of 17 late postoperative deaths, eight were sudden and nine were due to chronic heart failure. In particular, postoperative atrial fibrillation was a significant contributing factor to poor clinical outcome. Hence, while ventricular septal myotomy-myectomy is not always a curative procedure for obstructive hypertrophic cardiomyopathy, the vast majority of patients who survive operation experience long-lasting clinical improvement.

Abstract: The influx of calcium ions into the myocardial cell sets in motion a series of steps which end with contraction. Reduced intracellular calcium activity diminishes the contractile and mechanical function and thereby lowers myocardial oxygen demand. This is a beneficial effect when the myocardium is threatened by ischemia, such as occurs during transient coronary occlusion. We investigated the direct intracoronary injection of nifedipine, a known Ca2+ antagonist, immediately prior to transluminal angioplasty (PTCA). It was reasoned that the specific inhibitory action of nifedipine on contractile energy expenditure could provide temporary support for ischemic or potentially ischemic cardiac cells in that region during such induced interruption of flow. In order to test this hypothesis, the hemodynamic response was measured in 11 patients, first, to the injection of 0·2 mg nifedipine in the left main coronary artery, and second, to the transluminal occlusion of the stenosis for 45 s during PTCA. A second group of 14 patients was also studied for lactate production before and after PTCA of the left anterior descending artery (LAD) either with or without superselective intracoronary injection of nifedipine distal to the stenosis in the LAD. Coronary sinus (CSF) and great cardiac vein flow (GC yE), difference in lactate (A-GCV) and left ventricular isovolumic contraction (peak+/dP/dt, Vmax) were monitored. A 45 occlusion of LAD virtually eliminates all flow and induces severe ischemia accompanied by impairment of LV contractility and relaxation. Nifedipine i.c., while reducing the contractile and mechanical function of the anterior wall by a regional cardioplegic effect, increases the poststenotic flow. Lactate production in the great cardiac vein following (15 s) the LAD occlusion (TO) rose sharply. Such release is almost completely suppressed when transluminal occlusion was performed immediately after the i.c. administration of nifedipine (02 mg). It is postulated that the specific inhibitory action of nifedipine on contractile energy expenditure prevents ischemic cardiac cells from becoming anaerobic, during transluminal occlusion for periods lasting up to 90s. This may prevent them from acquiring damage, as a result of what otherwise must be termed a potentially beneficial procedure.

Abstract: Congestive heart failure is usually accompanied by cardiovascular signs of an increased sympathetic and a decreased parasympathetic efferent activity. A current hypothesis for these autonomic changes holds the baroreceptor mechanisms mainly responsible for this complex neural reflex pattern together with a decreased responsiveness of cardiac vagal afferent ffibers. An alternative hypothesis is proposed here. Afferent sympathetic fibers with sensory endings in the atria and in the pulmonary veins are progressively excited by volume load. In cats with a chronic spinal section at C8, breathing spontaneously, an infusion of saline induces a reflex tachycardia through a sympatho-sympathetic neural circuit. In chronic dogs with intact cardiovascular innervation, the stimulation of aortic or cardiac sympathetic afferent fibers elicits an excitatory sympathetic reflex leading to hypertension and tachycardia; in addition, the sensitivity of baroreflexes is markedly reduced. Therefore, in congestive heart failure, especially in the absence of hypotension, the reflex excitation of the sympathetic outflow and the inhibition of the vagal efferent activity directed to the heart could be due to reflex mechanisms mediated by sympathetic cardiovascular afferents.

Abstract: While it is well established that the acute haemodynamic effects of the beta blockers used in antihypertensive therapy vary considerably, it is still uncertain if this is true during chronic treatment. We have studied seven different beta blockers (one year follow-up): atenolol and metoprolol (cardioselective, without ISA), timolol (non-cardioselective, without ISA), and penbutolol, bunitrolol, alprenolol and pindolol (non-cardioselective, with different degrees of ISA). All drugs induced statistically significant reductions in heart rate (HR), cardiac output (CO) and blood pressure (BP) at rest as well as during exercise. During 100 and 150 W exercise CO and HR were generally decreased by 20–25% on beta blockers without ISA, less on beta blockers with strong ISA. Only in very few patients did total peripheral resistance (TPR) fall more than 10% below pre-treatment level both at rest and during exercise and TPR was not significantly reduced below pre-treatment level in any series. Drugs with combined beta-blocking and vasodilating (or alpha-blocking) properties (prizidilol and labetalol) induced clear reduction in TPR. HR was reduced, but since SI increased there was less reduction in CO on labetalol than on pure beta blockers and actually a small increase in CO on prizidilol.

Abstract: Heart muscle fibres always undergo severe functional and structural alterations, finally resulting in necrotization, if free extracellular Ca2+ ions penetrate abundantly through the sarcolemma membrane into the myoplasm, so that the capacities of the Ca2+ binding or extrusion processes become overpowered. The crucial reaction consists of high-energy phosphate exhaustion which is brought about (a) by excessive activation of Ca2+-dependent intracellular ATPases, and (b) by Ca2+ induced impairment of the mitochondria. Intracellular Ca2+ overload proved to the common denominator in the pathogenesis of severe myocardial fibre injury and death produced under the following circumstances: Overdoses of β-adrenergic catecholamines, dihydrotachysterol or vitamin D3 alimentary K+ or Mg2+ deficiency, hereditary cardiomyopathy of Syrian hamsters. Moreover, intracellular Ca2+ overload develops in the course of myocardial hypoxia or ischaemia thus causing additional precipitous damage of the mitochrondria. Following our first observations made in 1968, it has turned out that in all these cases, Ca2+ antagonists are capable of protecting myocardial cell integrity in that they prevent excessive transmembrane Ca2+ uptake. This is also true of the Ca2+ paradox: Ca2+ antagonists possibly inhibit the development of sarcolemmal leaks in the Ca2+ deprived myocardium. However, it is more likely that Ca2+ antagonists restrict the exaggerated influx of Ca2+ through these leaks, when the Ca2+ myocardial fibres return to a normal Ca2+ medium.

Abstract: Physiologic hypertrophy occurs as the result of exercise conditioning and is characterized by normal or supranormal left ventricular (LV) contractile function and reversibility of structural alterations. Whether hypertrophy produced by chronic abnormal loading can be termed 'physiologic' is a matter of debate because in experimental pressure overload hypertrophy normal in vivo ventricular function may be associated with abnormal in vitro function of the papillary muscles. In patients with moderate LV hypertrophy from aortic valve disease (angiographic mass less than 180 g/m2) ejection fraction (EF) is preserved, but at similar levels of afterload, when mass exceeds 180 g/m2, EF is depressed. Comparison of LV function with myocardial structure (endomyocardial biopsies) has shown that in patients with compensated LV function and those with left heart failure (EF less than 57%, LVEDP greater than 20 mm Hg and/or cardiac index less than 2.5 l/min/m2) interstitial fibrosis (IF) was increased to a similar extent (16 and 18%; normal less than 5%), whereas muscle fiber diameter (MFD; normal less than or equal to 20 mu) was larger (P less than 0.05) in the patients with failure (30 mu) than in those with preserved function (27 mu). Moreover patients with depressed postoperative function had a larger (P less than 0.01) preoperative MFD (35 mu) than those with normal postoperative function (30 mu). Seventeen months after successful aortic valve replacement IF increased (P less than 0.02) and MFD decreased (P less than 0.001) but did not become normal regardless whether postoperative function was normal or depressed. Thus in secondary hypertrophy myocardial structure is pathologic even in the presence of normal LV function and depressed function appears likely to be related to excessive fiber hypertrophy rather than to IF. Massive fiber hypertrophy heralds an unfavorable postoperative LV function and fibrosis is irreversible after surgical correction of the abnormal load.

Abstract: There is a major controversy over the relative value of anti-hypertensive drugs in hypertension in pregnancy. Our purpose was to study two different beta-adrenolytic drugs, atenolol, a cardioselective beta blocker, and labetalol, an alpha-beta blocker. Fifty-six hypertensive (BP greater than 140/90 mmHg) pregnant women were treated either with atenolol or labetalol. The patients were divided into two subgroups for which there were no statistical differences with regard to age, number of previous pregnancies, initial level of blood pressure and uricemia, proteinuric pre-eclampsia, beginning of therapeutic trial and delivery. The average daily dosage was 144.6 +/- 47.8 mg day-1 with atenolol and 614 +/- 47.8 mg day-1 with labetalol. This study shows: the same anti-hypertensive effect of the two drugs with control of blood pressure in 82% of the cases; a birth-weight significantly higher with labetalol (3280 +/- 555 g) than with atenolol (2750 +/- 630 g) (P less than 0.001); two still-births with atenolol; no adverse effects of the drugs during pregnancy and the neo-natal period; the trans-placental passage of atenolol and labetalol as shown by plasma dosages in the mothers and the new-born. It is concluded that atenolol and labetalol are safe and they are usually effective in the control of the hypertension complicating pregnancy. But labetalol appears to be better able to prevent the appearance of fetal growth retardation.

Abstract: During the last 10 years there has been a growing interest in the use of domestic pigs in the study of various aspects of myocardial ischemia. While most studies are still performed on dogs, a number of scientific and non-scientific (emotional) reasons have led to a shift from the use of the former to that of domestic pigs. In this paper the suitability of the pig for cardiovascular studies is dealt with, with special attention to the coronary and collateral circulation. A number of manifestations of myocardial ischemia and reperfusion of previously underperfused myocardium such as ventricular arrhythmias, metabolism and recovery of function are discussed. Where possible, the comparison is made with findings in the dog.

Abstract: Contraction-band necrosis, a striking morphologic lesion, is common to many types of myocardial injury including the calcium paradox and ischaemic injury with reperfusion. This lesion is characterized by explosive swelling, massive calcium overload, and severe disruption of the myofibrils due to the formation of contraction bands. The studies reviewed in this paper provide evidence that in ischaemia and reperfusion, these changes are preceded by sarcolemmal injury that occurs during the period of ischaemia. Sarcolemmal injury was evaluated by electron microscopy and by measurements of inulin diffusible space (IDS) in thin slices of myocardium incubated in vitro . Reversibly injured ischaemic myocvtes have ultra-structurally intact plasma membranes which are impermeable to inulin. Longer durations of ischaemia, sufficient to produce contraction-band necrosis during reperfusion. result in fragmentation of plasma membranes during the ischaemic intervals, and the IDS is markedly increased during subsequent incu bation. Thus ultrastructural evidence of membrane damage is present early in ischaemia and is associated temporally with the increased IDS. The role of anoxia, per s.c. in inducing membrane damage was in vestigated in tissue slices incubated at 37ΰC in crystalloidal media gassed with nitrogen. Anoxic slices produced lactate and lost ATP and adenine nucleotides, but cell volume and the IDS were not significantly increased for at least jive hours (twice the time required for severe membrane damage to develop in total ischaemia) and the plasmalemma remained intact by electron microscopy. Thus, despite depletion of high energy phosphates, membrane damage, detectable by alterations in IDS or ultrastructure, occurs much more slowly during anoxia alone than during ischaemia. These results suggest that anoxia, per Se, may not be the cause of membrane damage in ischaemia.

Abstract: Based on bicycle ergometer tests in 50 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 19 patients with hypertrophic non-obstructive cardiomyopathy (HNCM) if clinical (NYHA) class I to IV, the profile of several haemodynamic parameters (heart rate, stroke volume index, cardiac index, pulmonary artery pressure) during exercise was evaluated. The following pattern was found: (1) with increasing degree of clinical symptoms, the mean values of stroke volume decrease and the mean values of pulmonary artery pressure increase; (2) stroke volume does not show the normal increase during exercise in a considerable number of patients (48% of HOCM, 26% of HNCM patients); (3) failing increase in stroke volume is in part compensated by increase in heart rate; (4) pathological increase in mean pulmonary artery pressure correlates with severity of clinical symptoms, but even a considerable number of clinically asymptomatic patients exhibit extremely pathological pressure increase; (5) there is no fundamental difference of the behaviour of the measured haemodynamic parameters between HOCM and HNCM; (6) there is marked overlapping of exercise-induced haemodynamic changes between patients of different NYHA classes of clinical impairment. Therefore, measurements of exercise haemodynamics are necessary to define clearly the degree of functional impairment in the individual patient. Based on identically performed exercise tests in 53 patients with HOCM, the clinical and haemodynamic effects of medical therapy with propranolol (n = 12) or verapamil (n = 25) and of surgical treatment (n = 21) were compared. Maximal exercise capacity was on an average not changed after propranolol but increased after verapamil and, most significantly, after surgery. This could be attributed to corresponding haemodynamic changes, especially concerning cardiac output and pulmonary artery pressure. As a whole, verapamil was clinically and haemodynamically superior to propranolol, but not as effective as surgical treatment.

Abstract: The Ca2+ paradox is characterized by a rapid and uncontrolled entry of ca2+ Whilst the consequence of the resultant gain in Ca2+ are relatively well defined, uncertainty exists concerning the route of entry. Possible routes include passive diffusion across damaged sarcolemma and intercalated discs, active transport in exchange for K+ or Na+ and entry through the voltage-activated, Ca2+ slow channels. The following experiments were designed to differentiate between these possibilities. Isolated spontaneously beating Sprague-Dawley rat hearts were perfused at 37ΰC with Ca2+ perfusion buffer for >1 min before starting Ca2+ repletion. Adding 2–4 m mol l−1 Co2+ or Mn2+ before, during but not coincident with Ca2+ repletion protected against the paradox as indicated by an absence of myoglobin release and Ca2+ overload. Despite this protection marked distortion of the glycocalyx occurred, with splitting of the basement coat and blebbing. The intercalated discs, however, remained intact. It seems unlikely therefore that splitting of the basement coat necessarily results in an uncontrolled entry of Ca2+ Since Mn2+ and Co2+ block Ca2+ entry through the slow channels their failure to prevent the uncontrolled entry of Ca2+ when added at the time of Ca2+ repletion favours the view that Ca2+ entry during the paradox does not depend upon entry of Ca2+ through the slow channels. In other experiments hearts were preloaded with Na2+ to alter intracellular Na2+ before Ca2+ repletion. This procedure did not markedly affect the gain in Ca2+ These findings will be discussed in terms of the route(s) and consequence(s) of the uncontrolled entry of Ca2+ that occurs when Ca2+ is reintroduced after a period of Ca2+-free perfusion.

Abstract: Provocative tests for coronary spasm were performed in a group of 131 patients (124 men and 7 women) with recent (less than 6 weeks) transmural myocardial infarction. Coronary arteriography was performed 27 +/- 9 days after the onset of the infarction. The provocative test was performed using a single IV bolus of 0.4 mg of ergometrine. Aortic pressure, ECG and arteriograms of the two coronary vessels were repeated 3 and 5 min later. Provoked spasm was observed in 27 (21%) of the patients. In 13 (48%) the coronary spasm occurred in a vessel presumed to be responsible for the myocardial infarction, while it was observed in coronary artery unrelated to the area of the infarct in 14 (52% of the cases with spasm). Thus, this study demonstrates a high degree of reactivity of the coronary tree of patients with recent transmural myocardial infarction suggesting the likelihood of a role for spasm in the infarction process and offering some explanation for subsequent recurrent ischemic events.

Abstract: The effect of flecainide in 12 patients with the Wolff-Parkinson-White syndrome was analyzed with respect to the anterograde and retrograde conduction properties of the accessory pathway, the modes of initiation and termination of circus movement tachycardias, and the ventricular response during induced atrial fibrillation. The principal effect of this drug was to depress both anterograde and retrograde conduction of the accessory pathway. In 8/9 cases circus movement tachycardia was terminated by prolongation of the retrograde effective refractory period of the accessory pathway. Flecainide increased the shortest and the mean cycle length during induced atrial fibrillation. It is concluded that the drug may be of potential benefit in patients with paroxysmal supraventricular tachycardias in patients with the Wolff-Parkinson-White syndrome.

Abstract: The pathogenetic mechanisms of idiopathic long QT syndrome have been largely, although not completely, understood; however, several critical issues highly relevant to the clinical management of patients affected by the syndrome need to be clarified. For this purpose, physicians are invited to contribute to a registry of such patients

Abstract: In a total of 339 patients with hypertrophic cardiomyopathies (typical HOCM, n = 224, atypical HOCM, n = 30; HNCM, n = 80) the clinical course, the Sokolow-Lyon index in the ECG and the prognosis as demonstrated by cumulative survival rates were analysed to get more differentiated information for the characterization of these myocardial disorders. No change in the type of hypertrophic cardiomyopathy was found, indicating different clinical entities. No increase of the Sokolow-Lyon index was observed during follow-up. Only a small proportion of patients seemed to benefit from treatment with propranolol. Surgical treatment appears to be the therapy of choice, at least in the advanced stage of the disease refractory to medical treatment. In addition, strong evidence was obtained that surgical treatment improved the prognosis in patients with typical HOCM.

Abstract: Several phenothiazines were found to provide significant protection against loss of tissue creatine phosphokinase caused by the calcium paradox. The concentration of phenothiazine required for protection lies within the range generally attributable to their calmodulin inhibition properties. Moreover, the order of effectiveness in protecting the calcium overloaded myocardium is consistent with their potency as calmodulin inhibitors (trifluoperazine greater than chloropromazine greater than promethazine). The most potent calmodulin inhibitor was shown to dramatically reduce the amount of creatine phosphokinase loss from calcium depleted hearts exposed to buffer containing calcium under anoxic conditions. On the other hand, the drug failed to alter the oxygen-dependent component of the calcium paradox. It also failed to prevent the proteolytic conversion of xanthine dehydrogenase to xanthine oxidase. The possibility that calmodulin activation promotes cellular damage by activating either directly or indirectly specific membrane cellular phospholipases is discussed. Also discussed is the hypothesis that oxygen-dependent damage may be linked to the generation of superoxide anion by the enzyme xanthine oxidase.

Abstract: Out of 178 consecutive patients with acute inferior wall myocardial infarction submitted to technetium-99 m pyrophosphate scintigraphy, 49 (27.5%) were found to have concomitant right ventricular infarction. Gated blood pool scans showed right ventricular abnormalities in 21 out of 26 patients who were submitted to this investigation (right ventricular asynergy: 16 cases; right ventricular dilatation: eight cases; decreased right ventricular ejection fraction: 16 cases). Complications were common in the acute stage. Shock was noted in 19 cases (eight related to bradycardia, three related to relative hypovolaemia and eight instances of true cardiogenic shock). Atrial fibrillation (seven patients), ventricular fibrillation (eight patients) and severe atrioventricular conduction disorders (13 patients) were also frequent. In spite of this, the in-hospital mortality was low: three deaths occurred (6.1%), one from heart failure, two others from posterior septal rupture. All patients were followed up for one year or more. Six additional deaths were noted (three from left cardiac failure, two from recurrent anterior wall infarction and one from massive pulmonary embolism). Clinical assessment, haemodynamic measurements and gated blood pool scans showed significant improvement of right ventricular function with return to normal in those cases with small right ventricular infarcts as judged from technetium-99 m pyrophosphate scintigraphy. In spite of the complications seen in the initial period, patients with a right ventricular infarction have a good overall prognosis and the long-term outcome, primarily determined by the left-sided lesions, is often favourable.

Abstract: Preischaemic doubling of the myocardial buffer capacity optimizes the energy supply of the ischaemic heart by anaerobic glycolysis. For osmotic reasons this method of improving ischaemia tolerance can only be realized in combination with cardioplegia by extracellular Na+ and Ca2+ reduction. The cardioplegic solution 'HTK' which has been developed according to these considerations. (1) delays the decay velocity of myocardial ATP by a factor of 7-8 in comparison with pure ischaemia; (2) leads to a good myocardial recovery with regard to metabolic, morphological, and functional criteria after an ischaemic stress of 300 min at 23 +/- 1 degrees C--especially after the addition of quinine; (3) is considerably reduced in its protective efficacy by adding 50 mumol l-1 Ca2+; (4) causes a calcium paradox if it is infused for 30 min at 35 degrees C; this does not happen if it is infused for 60 min at 25 degrees C or for 120 min at 15 degrees C; on adding 50 mumol l-1 Ca2+ to the solution the risk of a calcium paradox is significantly reduced, even after infusion for 35 min at 35 degrees C; (5) effects an evident delay of recovery, if a continuous ischaemic stress of 300 min at 23 degrees +/- 1 degree C is reduced to 3 X 100 min of ischaemia at 17 +/- 1 degrees C by intermittent cardioplegic reperfusion; (6) considerably improves the myocardial recovery even after intermittent cardioplegia if 50 mumol l-1 Ca2+ are added or Mg2+ is reduced from 9 to 4 mmol l-12. The metabolic, morphological, and functional results are equivalent to those after 300 min of continuous ischaemia. Further investigations must show to what extent the 'membrane stabilizing effect' of [Ca2+]o can be achieved by taking advantage of mutual ionic interaction on the level of plasmalemma (e.g. H+-Mg2+-Ca2+) or by adding membrane effective substances (quinine).

Abstract: Cardiac pumping action is governed by two interdependent systems: those that govern contraction and the emptying of the heart (inotropic) and those that control its relaxation and filling (lusitropic). The signs and symptoms of ‘heart failure’ can be caused by abnormalities of either or both of these systems. Major technological advances in the evaluation of the cardiac patient, especially those that utilize measurements of ventricular volume, coupled with potent new drugs that can modify differently the inotropic and lusitropic properties of the myocardium, make it necessary to understand the role that each plays in the genesis of the clinical syndrome of heart failure.

Abstract: Both the electrophysiological and antiarrhythmic effects of some antiarrhythmic agents may differ markedly depending on their route of administration. Flecainide acetate, a new class 1 agent, was therefore administered both intravenously and orally to 13 patients with recurrent paroxysmal tachycardia to assess whether the acute response to intravenous flecainide accurately predicts the response to oral therapy. Eight patients had atrioventricular re-entrant tachycardia (AVRT) and five patients intra AV nodal re-entrant tachycardia (AVNRT). When administered by either route, flecainide markedly prolonged both the anterograde and retrograde conduction intervals during constant rate pacing and the anterograde and retrograde Wenckebach cycle lengths during incremental pacing. Five of the 13 patients developed complete retrograde block after both routes of administration of the drug. All 13 patients received intravenous flecainide during tachycardia with successful reversion to sinus rhythm in all cases. Tachycardia could be reinitiated in five of the patients with AVRT after intravenous flecainide and in one further patient after oral administration. It was not possible to reinitiate tachycardia in any of the five patients with AVNRT after either intravenous or oral flecainide. The size of the tachycardia initiation windows, by either atrial or ventricular premature stimuli, were significantly reduced by both intravenous and oral flecainide. In those patients in whom tachycardia could be reinitiated, tachycardia cycle length was significantly increased, and to a similar degree, by both routes of administration of the drug. This increase in cycle length was predominantly due to prolongation in retrograde conduction. It is concluded that flecainide acetate is a potent antiarrhythmic agent for use in patients with junctional tachycardia. The intravenous administration of flecainide reliably predicts the subsequent response to oral therapy.

Abstract: The causes of sudden, unexpected death in highly-conditioned competitive athletes are summarized. In the vast majority of young athletes (less than 35 years of age) sudden death is due to underlying structural cardiovascular disease. Hypertrophic cardiomyopathy appears to be the most common cause of such deaths and may account for about one-half of the sudden deaths in a youthful athletic population. Cardiovascular abnormalities that appear to be less frequent important causes of sudden death include anomalous origin of the left coronary artery from the anterior sinus of Valsalva, ruptured aorta (due to cystic medial necrosis), idiopathic concentric left ventricular hypertrophy and coronary artery atherosclerosis. Other diseases which are probably particularly uncommon causes of sudden death in the young athlete include mitral valve prolapse, aortic valvular stenosis, acute myocarditis, QT interval prolongation syndromes, hypoplasia of the coronary arteries or sarcoidosis. Cardiovascular disease in young athletes is usually unsuspected during life. In only about 25% of those competitive athletes who die suddenly is underlying disease identified prior to participation and rarely is the correct clinical diagnosis made. In contrast, when sudden death occurs in older competitive or recreational athletes (over 35 years of age) it is usually due to coronary artery disease.

Abstract: The Dusseldorf surgical series of patients with hypertrophic obstructive cardiomyopathy (HOCM) (1963-82) comprises 137 patients, of whom 123 had typical HOCM and 14 atypical midventricular stenosis. Indications for surgery were unsatisfactory response to drug therapy and clinical symptoms according to at least functional class III (NYHA). The predominant approach for the relief of both types of HOCM was transaortic (112 cases; two deaths = 1.8%). The hospital mortality of the total series was 6.6% (nine of 137 patients). The most severe problems were caused by additional acquired mitral valve lesions. There is no special risk for patients with atypical midventricular HOCM. The systolic gradient between left ventricle and aorta could be removed or diminished in all cases.

Abstract: The short-term efficacy of diltiazem (D) has been compared to that of propranolol (P), in a group of 70 patients hospitalized in the Coronary Care Unit for unstable angina, defined as recent (less than one month) appearance or aggravation of spontaneous chest pains. Among the 70 patients, 24 had angina only at rest. The patients have been divided into two groups according to ST- T changes during chest pain: 29 with ST elevation (group A) and 41 with other repolarization abnormalities (group B). Treatment was then randomized in each group Treatment was considered successful only if spontaneous chest pains disappeared completely. Thirty-four patients were treated with D (282±102 mg/day) and 36 with P (158±81 mg/day). In the whole group and in groups A and B considered individually, responses to D and P did not differ. Among the 24 patients with angina exclusively at rest, nine successes and four failures were observed with D. There was no symptomatic relief among the 11 patients treated by P (P = 0.001). Moreover, the number of episodes of angina was decreased by D and unchanged by P, while eight out of the 11 failures with P were immediate successes when treatment was replaced with D. These results suggest that D is preferable to P for management of unstable angina in patients with angina which is exclusively spontaneous.

Abstract: HNCM tends to have more diffuse or generalized hypertrophy than HOCM, although these two types are not fundamentally different in aetiology (genetic). Extreme ASH is primarily related to a hereditary factor while HNCM, including apical hypertrophy, seems to be based on an abnormal disposition to produce myocardial hypertrophy in response to endogenous or exogenous stimulation such as catecholamines, chronic anoxia, hypertension or even aging. Hypertension by itself, however, can not be a cause of apical hypertrophy. The configuration of left ventricular hypertrophy in HCM can be divided roughly into several patterns: ASH, apical, postero-inferior, generalized or diffuse types, etc. ASH is not an essential morphology for HNCM. Apical hypertrophy is the only specific hypertrophic pattern which shows characteristic ECG abnormalities (giant negative T waves and high QRS voltage in left precordial leads). Inverted T waves combined with high QRS voltage tends to be a reflection of a localized hypertrophic portion in the left ventricular free wall. Abnormal Q waves associated with left axis deviation usually suggest marked septal hypertrophy. They seem to be related to conduction disturbances in myopathic septum.

Abstract: Macroscopically asymmetric hypertrophy of the interventricular septum is the characteristic change, though mild degrees can be seen in normal hearts and in combination with congenital or acquired heart disease. If asymmetric hypertrophy is severe, this alone characterises the condition. Concentric forms have, however, been described. At light microscopic level disarray and often extreme hypertrophy of myocardial fibres together with degenerative changes and interstitial fibrosis are typical. Overlap of individual features with ‘ordinary’ hypertrophy exists but if all criteria are considered in combination a high degree of diagnostic reliability can be achieved, frequently aided by severe accumulation of glycogen. In support semiquantitative studies will also be presented. The patterns of abnormal fibre arrangement differ in the two clinical types. In cases with obstruction the abnormal fibres are predominantly confined to the interventricular septum, whereas in cases without obstruction they are scattered focally throughout the ventricular walls. Unfortunately, these disturbances are not always present. Subdivisions based on histological changes by other workers will be mentioned. Brief reference will be made to experimental work that has shown that a possible endogenous mechanism may be operative in some of the patients with hypertrophic cardiomyopathy. It is concluded that the morphology of hypertrophic cardiomyopathy is sufficiently characteristic to separate it as a distinct entity and to ensure reliable diagnosis.