Prevalence and incidence of hyperkalaemia in the Spanish population with heart failure with reduced ejection fraction: a systematic review and populational relevance. / Prevalencia e incidencia de hiperpotasemia en población española con insuficiencia cardiaca con fracción de eyección deprimida: revisión sistemática y relevancia poblacional.

BACKGROUND AND OBJECTIVES: Hyperkalaemia (K+ levels≥5.5mmol/L) is a severe ion imbalance that occurs in patients who have heart failure (HF) with reduced ejection fraction (HFrEF) and increases the risk of ventricular fibrillation. Given that there are no estimates on the number of patients with this complication, the aim of this study was to estimate the prevalence and incidence of hyperkalaemia in patients with HFrEF in Spain. MATERIAL AND METHODS: Based on a systematic literature search and through a meta-analysis, we calculated an HFrEF prevalence of ≤40% in the European and U.S. POPULATION: Based on another systematic literature search, we calculated the prevalence of hyperkalaemia in patients with HF and its annual incidence rate. Considering the previous values and the Spanish population pyramid in 2016, we estimated the number of individuals with HFrEF who currently have hyperkalaemia and those who develop it each year in Spain. RESULTS: Approximately 17,100 (10,000 men and 7100 women) of the 508,000 patients with HFrEF in Spain have hyperkalaemia. Furthermore, approximately 14,900 patients with HFrEF (9500 men and 5400 women) develop hyperkalaemia each year. CONCLUSIONS: Approximately 1 of every 30 patients with HFrEF has plasma potassium values >5.5 mmol/L.

Umbilical cord blood-derived stem cells spontaneously express cardiomyogenic traits.

BACKGROUND: Umbilical cord blood (UCB) has been widely used for hematopoietic stem cell transplantation. The UCB-derived stem cells (UCBSCs) have been proposed as an alternative to bone marrow (BM)-derived mesenchymal stem cells (MSCs) for cardiac cell-based therapy. Herein we studied whether UCBSCs spontaneously exhibit cardiac-specific markers in vitro. METHODS: Human UCBSCs were isolated, expanded, and phenotyped by flow cytometry, quantitative RT-PCR, and immunofluorescence. Cell pluripotency and proliferation were also assessed by adipogenic and osteogenic media and in growth assays. RESULTS: Among 25 analyzed UCB, 16% of cases afforded primary culture satisfactory generation of UCBSCs. Duplication time (Td) of cultures was 2.16 +/- 0.06 days. The cells were strongly positive for CD105 (18.5 +/- 0.14), CD44 (27 +/- 2.8), CD166 (13 +/- 9), CD29 (59 +/- 9.4), CD90 (60 +/- 11) and consistently negative for CD117 (1.2 +/- 0.1), CD106 (1.1 +/- 0), CD34 (1.2 +/- 0.2), CD14 (1 +/- 0), and CD45 (1 +/- 0), consistent with a mesenchymal lineage. Adipogenesis and osteogenesis of cells resulted in low accumulation of intracellular lipid droplets and high deposition of calcium. The UCBSCs showed gene transcripts for alpha-actinin, connexin (Cx)-43, SERCA-2, and stromal cell-derived factor (SDF)-1alpha. At the protein level, the cells abundantly expressed alpha-actinin, Cx-43, SERCA-2 and SDF-1alpha. In contrast, these cells did not express the cardiac transcription factors GATA-4, Tbx5, and Nkx2.5, nor the sarcomeric proteins beta-myosin heavy chain (beta-MyHC) or cardiac troponin I (cTnI). CONCLUSIONS: Human UCBSCs may represent an alternative source of stem cells for myocardial-cell replacement. These cells can be highly expanded. They spontaneously express proteins of paramount importance for cardiovascular regeneration, such as Cx-43, SERCA-2, and SDF-1alpha.

Ventricular arrhythmias and local electrograms after chronic regional denervation of the ischemic area in the pig heart.

Cardiac denervation has been proved to reduce the incidence of coronary occlusion arrhythmias in digs, but the effect of limiting the extent of sympathectomy to the ischemic area, particularly in hearts with sparse coronary collateral circulation, as in the human heart, needs further investigation. Ventricular arrhythmias and changes in epicardial direct current electrograms induced during acute left anterior descending coronary artery occlusion were recorded in 14 pigs subjected to regional denervation of the ischemic area 2 weeks before; these were compared with findings in 14 sham-operated control pigs. Regional denervation was induced by pericoronary application of phenol above the occlusion site and it was confirmed by the loss of myocardial catecholamine histofluorescence. During 35 min of ischemia, significant differences in occurrence of ventricular premature beats, ventricular tachycardia, ST segment elevation, TQ segment depression and epicardial activation delays were observed between the two groups of experiments, with lower values of each variable in the denervated hearts. Ventricular fibrillation occurred 32 times in 11 control pigs and only 15 times in eight denervated hearts. In contrast, programmed ventricular extrastimuli delivered during 35 to 50 min of ischemia induced 39 fibrillatory episodes in 13 denervated hearts and only 14 episodes in seven control pigs. Thus, denervation limited to the ischemic area in hearts with a human-like coronary artery pattern was associated with a decrease in the magnitude of early ischemic arrhythmias and electrocardiographic alterations, but the procedure was unable to prevent early induction of ventricular fibrillation.

Predisposing factors and prognostic value of sustained monomorphic ventricular tachycardia in the early phase of acute myocardial infarction.

OBJECTIVES: The purpose of the study was to analyze the factors that favor the occurrence of sustained monomorphic ventricular tachycardia in the early phase (< 48 h) of acute myocardial infarction and to establish its prognostic implications. BACKGROUND: Sustained monomorphic ventricular tachycardia early in the course of an acute myocardial infarction is an uncommon arrhythmia, and its significance has not been specifically studied. METHODS: The clinical characteristics and prognosis of sustained monomorphic ventricular tachycardia were studied in 21 (1.9%) of 1,120 consecutive patients admitted to the coronary care unit with a diagnosis of myocardial infarction. RESULTS: Patients with sustained monomorphic ventricular tachycardia had a larger infarct on the basis of peak creatine kinase, MB fraction (CK-MB) isoenzyme activity (435 +/- 253 IU/liter vs. 168 +/- 145 IU/liter, p < 0.001) and higher mortality rate (43% vs. 11%, p < 0.001). By logistic regression analysis, independent predictors of sustained monomorphic ventricular tachycardia were CK-MB (odds ratio [OR] 11.8), Killip class (OR 4.0) and bifascicular bundle branch block (OR 3.1). Moreover, sustained monomorphic ventricular tachycardia was itself an independent predictor of mortality (OR 5.0). Compared with patients with ventricular fibrillation, those with sustained monomorphic ventricular tachycardia had a worse Killip class (Killip class > I: 63% vs. 30%, p < 0.05), higher CK-MB activity (430 +/- 260 IU/liter vs. 242 +/- 176 IU/liter, p < 0.01) and higher arrhythmia recurrence rate (31% vs. 4%, p < 0.01). During the follow-up period, 5 (42%) of 12 survivors in the sustained monomorphic ventricular tachycardia group died of cardiac-related causes. Recurrence of ventricular tachycardia was seen in two patients (17%). CONCLUSIONS: Sustained monomorphic ventricular tachycardia during the first 48 h of myocardial infarction is a sign of extensive myocardial damage and an independent predictor of in-hospital mortality.

Identification of cardiomyogenic lineage markers in untreated human bone marrow-derived mesenchymal stem cells.

BACKGROUND: Recent reports refute the classic paradigm by which human heart is unable to repair itself following disease or injury. Cardiac and noncardiac stem cells with cardiac regeneration potential have been documented. We studied whether untreated mesenchymal stem cells express markers of cardiomyogenic lineage in vitro. METHODS: Mesenchymal stem cells were obtained from human iliac crest marrow aspirates. Cells were isolated and characterized using flow cytometry by surface expression of CD105, CD166, CD29, CD44, CD14, and CD34. To evaluate their cardiomyogenic potential, presence of cardiac proteins (cardiac troponin I, sarcomeric alpha-actinin, beta myosin heavy chain (beta-MyHC), connexin-43, and SERCA-2), and transcription factors (GATA-4) were assessed. RESULTS: Mesenchymal stem cells expressed CD105 (4.25 +/- 0.35), CD166 (27.83 +/- 1.89), and CD29 (9.4 +/- 0.57) and were negative for CD34, CD14, and CD45. In absence of additional stimuli in the culture media, these cells expressed connexin-43, alpha-actinin, and GATA-4, and were negative for SERCA-2, cardiac troponin I, and beta-MyHC. CONCLUSIONS: Human adult mesenchymal stem cells spontaneously exhibit markers of cardiac phenotype in vitro. In the appropiate myocardial environment, these cells may transdifferentiate into mature cardiomyocytes.

Cardiovascular reflex responses induced by epicardial chemoreceptor stimulation.

The cardiac mechano- and chemoreceptors are broadly distributed in the myocardium and coronary vessels. A portion of these receptors extends over the epicardium and pericardium and therefore can be excited by mechanical or chemical stimuli directly applied to the surface of the heart. Excitation of epicardial receptors by topical application of chemical compounds elicits a variety of reflex cardiovascular responses, without the vascular or systemic effects of the drug administered systemically. A considerable number of studies has used the epicardial sensory field as a tool to delineate the functional characteristics of the cardiac afferent neurones in normal as well as in pathological conditions. In this review we analyze the cardiovascular reflex responses induced by epicardial application of a variety of substances like bradykinin, nicotine, muscarine, isoprenaline, adenosine, potassium chloride, capsaicin, prostaglandins or substance P in physiological models and also in models with acute myocardial ischemia or heart failure. The data highlight the contribution of the epicardial sensory neurites to the overall control of the cardiovascular system and, on the other hand, strengthen the need for further investigations directed to better elucidate the reflex cardiovascular responses that may develop in patients with pericardial abnormalities.

Progressive mechanical impairment associated with progressive but reversible electrocardiographic ischaemic changes during repeated brief coronary artery occlusion in pigs.

Epicardial and endocardial electrograms, myocardial metabolism, left ventricular pressure, and regional myocardial tension were studied during 15 min coronary occlusions followed by 45 min reperfusion in the in situ pig heart to evaluate their reproducibility and the possibility of a cumulative effect. Two coronary occlusions were performed in 27 animals, three in 21, and four in nine. Throughout the different occlusions there was a progressive increase in peak TQ-ST segment shift, a progressively higher incidence of ST segment alternans, and an increasing prolongation of the ventricular activation time. Regional myocardial tension in the ischaemic area, measured in eight pigs, declined progressively after each occlusion-reperfusion cycle, whereas it failed to change in four sham experiments. Nevertheless, complete electrical recovery ensued after each reperfusion and was progressively quicker throughout the four reperfusions. In addition, lactate production due to ischaemia returned to extraction after each reperfusion when studied in eight pigs undergoing three occlusion-reperfusion cycles. It is concluded that multiple coronary occlusions in pigs causes (a) a progressive deterioration in contractility and (b) a progressive but reversible deterioration in the electrically changes. These findings may explain the impaired segmental wall motion seen in some patients with recurrent angina at rest and no evidence of infarction. In this model, the electrical and metabolic recovery after each reperfusion probably indicates that the gross ischaemic alterations were reversed but that a minor though probably increasing degree of tissue necrosis may have been present.

Effects of anaesthesia on acute ischaemic arrhythmias and epicardial electrograms in the pig heart in situ.

STUDY OBJECTIVE: The aim of the study was to assess the influence of general anaesthesia on electrocardiographic and arrhythmogenic responses to left anterior descending coronary artery occlusion. DESIGN: Pigs weighing 18-20 kg were anaesthetised with alpha chloralose 100 mg.kg-1 (n = 9) or thiopentone 30 mg.kg-1 (n = 9) and the arrhythmogenic effects of coronary artery occlusion were examined by sequential electrocardiographic measurements every 5 min and arrhythmia analysis every minute over a 60 min period. RESULTS: alpha Chloralose predisposed to lower ST segment elevation (analysis of variance for repeated measurements p less than 0.002), less marked epicardial conduction delay (p less than 0.01) with slower progression to monophasic potentials, and in contrast, to a greater number of episodes of ventricular premature beats (p less than 0.005), ventricular tachycardia (51 v 32 episodes), and ventricular fibrillation (6 v 2 pigs) than barbiturate anaesthesia. CONCLUSIONS: alpha Chloralose and barbiturates exerted opposite electrocardiographic and arrhythmogenic effects in a porcine model of acute myocardial ischaemia. Due to its proarrhythmic effect chloralose should probably be used in studies dealing with spontaneous and induced ischaemic arrhythmias.

Induced ventricular arrhythmias in regionally denervated porcine heart with healed myocardial infarction.

STUDY OBJECTIVE: The aim was to test the hypothesis that chronic sympathetic denervation of the boundaries of a healed myocardial infarction may modify the arrhythmogenic response to programmed electrical stimulation. DESIGN: Electrical induction of ventricular arrhythmias and infarct size were evaluated in a control group of pigs with a one month old myocardial infarction induced by ligature of the left anterior descending coronary artery below the first diagonal branch. These were compared with a group of similarly infarcted pigs subjected to regional denervation of the peri-infarction area induced by topical pericoronary application of phenol. Denervation was verified by the absence of adrenergic histofluorescent reaction to glyoxylic acid in myocardial samples. EXPERIMENTAL MATERIAL: 24 pigs (weight 15-20 kg) with myocardial infarction were studied, 13 of which were subjected to regional peri-infarction denervation, and 11 acted as controls. MEASUREMENTS AND MAIN RESULTS: Programmed ventricular stimulation with one to four extrastimuli at 500 and 400 ms basic cycle length at the left and right ventricles induced fewer episodes of ventricular fibrillation in the denervated than in the non-denervated group (five episodes in three pigs v 14 in nine pigs, p less than 0.005), but more episodes of sustained ventricular tachycardia (79 in eight pigs v 23 in two, p less than 0.001). Unlike fibrillation, induction of ventricular tachycardia increased with multiple extrastimuli and with short basic cycle length. The denervated preparations tended to develop smaller infarcts but this difference was not statistically significant: infarct weight (g) relative to total ventricular mass (g) = 7.2 (SD 2.4)% v 10.5(4.5)%. CONCLUSIONS: Neural integrity of the non-ischaemic myocardium bordering a healed infarction modulates inducibility of ventricular tachycardia and fibrillation during programmed ventricular stimulation.

Coronary denervation attenuates coronary constriction induced by muscarinic receptor stimulation in pigs.

OBJECTIVES: We tested the hypothesis that coronary denervation attenuates the reactivity of the coronary vessel to cholinergic stimulation. METHODS: Heart rate, left ventricular (LV) pressure, LV dP/dt, coronary blood flow at the left anterior descending (LAD) coronary artery, and epicardial ECG mapping were measured before and after topical application of 1% methacholine to the LAD in 10 pigs anesthetized with alpha-chloralose (100 mg/kg, i.v.); these were compared with 10 other pigs submitted 2 weeks previously to a denervation of the LAD with phenol. Coronary denervation was confirmed in all cases by adrenergic histofluorescence and by acetyl-cholinesterase staining. Isolated LAD rings from 10 additional pigs (5 controls and 5 treated with phenol) were stimulated with endothelin-1 to verify whether phenol affected coronary reactivity to noncholinergic stimulation. RESULTS: Methacholine induced a fall in coronary blood flow (10.3 +/- 5.3 ml/min vs 4.8 +/- 6.2 ml/min, ANOVA: P < 0.001), a drop in systolic LV pressure (113 +/- 19 mmHg vs 93 +/- 19 mmHg, P < 0.001) and LV dP/dt (1608 +/- 363 mmHg/s vs 1203 +/- 302 mmHg/s, P = 0.02) and elevation of the ST segment (1.4 +/- 0.9 vs 11.1 +/- 4.7 mV, P < 0.001) in controls. These changes were not preceded by heart rate variations and were inhibited by atropine. As compared to controls, phenol-treated pigs showed a smaller decline in coronary blood flow (13.1 +/- 4.5 ml/min to 10.4 +/- 5.4 ml/min, P < 0.001), a lower drop in LV pressure (107 +/- 20 mmHg to 100 +/- 19.7 mmHg, P < 0.001) and lesser ST segment elevation (2.2 +/- 1.7 mV to 5.6 +/- 4.2 mV, P < 0.001). Isolated LAD rings contracted after exposure to endothelin-1 in both controls and phenol-treated pigs (3.5 +/- 0.7 g vs 2.4 +/- 1.0 g, P = 0.06). CONCLUSIONS: Coronary denervation attenuates coronary constriction induced selectively by direct muscarinic receptor stimulation in the in situ pig heart.

Reperfusion arrhythmias after chronic regional denervation of the ischaemic myocardium in pigs.

OBJECTIVE: The aim was to assess the effects of chronic regional denervation of the ischaemic myocardium on reperfusion arrhythmias in a model with sparse coronary collateral circulation. METHODS: Baseline ventricular refractoriness and epicardial activation times were measured together with reperfusion arrhythmias after 15 min (I-15') or 30 min (I-30') of left anterior descending coronary artery occlusion in 38 barbiturate anaesthetised open chest pigs. Twenty pigs (11 in I-15' and nine in I-30') had a chronic (two week) denervation of the left anteroseptal region, whereas 18 pigs (10 in I-15' and eight in I-30') were sham operated (non-denervated) controls. Denervation was induced by pericoronary application of phenol and verified by absence of adrenergic histofluorescence. RESULTS: As compared with controls, denervated pigs showed: (1) longer activation times: 20.3 (SD 5.2) ms v 16.5 (4.6) ms, p < 0.001; (2) slightly longer refractory periods: 348(28) ms v 334(27) ms; (3) a tendency to lower postreperfusion ectopic activity: ectopic beats divided by time free of ventricular tachycardia: 0.13(0.19) v 0.34(0.40) in I-15', and 0.21(0.24) v 0.39(0.44) in I-30'; (4) slower ventricular tachycardia in I-30': 140(29) beats.min-1 v 185(29) beats.min-1, p < 0.009; and (5) comparable incidence of postreperfusion ventricular fibrillation: 4/11 pigs v 2/10 in I-15', and 5/9 v 4/8 in I-30'. CONCLUSIONS: Selective chronic denervation of the ischaemic myocardium was unable to protect against malignant reperfusion arrhythmias in hearts with human-like coronary collaterals. This was confirmed at two ischaemic periods known to produce progressive catecholamine accumulation and increased adrenoceptor density in the ischaemic myocardium.

Lack of evidence of M-cells in porcine left ventricular myocardium.

OBJECTIVE: The aim of this study was to analyze whether cells with long action potential duration, fast Vmax, and spike-and-dome configuration (M-cells) are present in porcine left ventricular myocardium. METHODS: Transmembrane action potentials (n = 505) of the left ventricle were recorded with conventional glass microelectrodes in an epicardial-endocardial direction at 2000 ms basic cycle length in 14 pigs. In 3 pigs, potentials were obtained at 1000, 2000, and 5000 ms cycle length before and after superfusion with quinidine HCl 1 microgram/ml. In addition, transmembrane potentials (n = 52) were recorded in 4 dogs at 2000 ms cycle length to verify the ability of our protocol to detect M-cells. RESULTS: In pigs, action potential duration at 90% repolarization was shorter (ANOVA, P < 0.001) and Vmax slower (P < 0.001) in the epicardium than in the other transmural sites, but there were no regional differences in resting membrane potential or in action potential amplitude. Potentials with particularly long phase 3 or with spike-and-dome configuration were not observed. All myocardial sites displayed rate dependence of action potential duration (P = 0.02) which was transmurally homogeneous and persisted after quinidine exposure. The drug did not induce afterdepolarizations. In dogs, potentials with spike-and-dome configuration, long duration, and fast Vmax, like those described in M-cells, were detected in deep epicardial and midmyocardial areas. CONCLUSION: The porcine left ventricular myocardium shows transmural differences in action potential duration and Vmax, but, unlike dogs, it lacks M-cells.

Neurally mediated depressor hemodynamic response induced by intracoronary catheter balloon inflation in pigs.

OBJECTIVES: To assess whether intracoronary catheter balloon inflation triggers a neurally mediated hemodynamic response that interacts with the ischemia-induced myocardial dysfunction. METHODS: Forty-eight chloralose anesthetized pigs underwent a 60 s intraluminal catheter balloon inflation of the proximal left anterior descending (LAD) coronary artery before and after one of these treatments: disruption of LAD pericoronary nerves with phenol (n=6), bilateral stellectomy (n=8), bilateral cervical vagotomy (n=6), atropine (n=5), and ganglionic blockade with hexamethonium (n=10). In 13 other pigs, we assessed the reproducibility of two balloon inflations spaced 15 min (n=6) or 60 min (n=7). The ECG, left ventricular (LV) pressure, and LV dP/dt were recorded during each intervention. Right ventricular (RV) pressure, RV dP/dt, and aortic blood flow were also measured in a subset of pigs. RESULTS: Balloon inflation induced an early (10 s) and reproducible (ANOVA, P<0.001) drop in systolic pressure and peak dP/dt; a decrease in aortic blood flow; a rise in end-diastolic pressure; and elevation of the ST segment. Pericoronary denervation, stellectomy and ganglionic blockade attenuated (P<0.001) the drop in LV parameters during coronary inflation, but atropine and vagotomy did not. CONCLUSIONS: A depressor hemodynamic response subserved by pericoronary nerves worsens the LV dysfunction induced by brief coronary catheter balloon inflation in anesthetized pigs. Cholinergic fibers do not appear to play a major role.

Low incidence of ventricular arrhythmias induced by ischaemia at the borders of a chronic infarct in a model with local postinfarction denervation.

OBJECTIVE: The aim was to assess the arrhythmogenic potential of acute ischaemia superimposed at the borders of a chronic myocardial infarct and to analyse the effects of myocardial necrosis on local autonomic innervation in pigs. METHODS: Ventricular arrhythmias were measured in alpha chloralose (100 mg.kg-1) anaesthetised open chest pigs during 60 min occlusion of the left anterior descending coronary artery 2 cm above the first diagonal branch (group I, n = 11) or just below this branch (group II, n = 12). These arrhythmias were compared with those induced in pigs with a one month old anteroseptal infarction (coronary ligature as in group II) submitted to a second occlusion 2 cm above the first (group III, n = 12). The area at risk after high or low ligature was measured in 12 control pigs using fluorescein. Sympathetic and parasympathetic innervation of the anteroseptal myocardium was studied in three pigs with a chronic anteroseptal infarction and in six pigs without infarction using adrenergic histofluorescence and acetylcholinesterase reaction. RESULTS: Compared with ischaemia alone, ischaemia at the borders of a chronic infarct induced a lower incidence of ventricular fibrillation (1/12 pigs v 11/11 in group I, p < 0.001, or 6/12 in group II, p < 0.05) and a tendency towards a lower occurrence of ventricular tachycardia (2/12 pigs v 8/11 in group I, p = 0.01, and 4/12 in group II) and fewer ventricular premature beats (mean number: 105 in group I v 30 in group III, p < 0.05). The mass of the ischaemic regions after low or high occlusion was 13.3(SD 3.0) g and 23.2(5.8) g, respectively. Adrenergic and cholinergic denervation was observed inside the necrotic area, along the subendocardium surviving the necrosis, and in a band of normal bordering myocardium [width: 3.2(2.0) mm for adrenergic and 2.1(1.2) mm for cholinergic denervation]. CONCLUSIONS: Acute ischaemia at the borders of a chronic anteroseptal infarct has a low arrhythmogenic potential in pigs. In this model the peri-infarction zone shows a band of sympathetic and parasympathetic denervation secondary to the necrosis.

Passive transmission of ischemic ST segment changes in low electrical resistance myocardial infarct scar in the pig.

OBJECTIVES: To analyze the passive electrical properties of a healed infarction and assess their role on transmission of contiguous ischemic ST segment potential changes. METHODS: We measured tissue resistivity (omega cm) at 1 kHz and the epicardial ST segment during 1 h of proximal reocclusion of the left anterior descending (LAD) coronary artery in 12 anesthetized pigs with one-month-old transmural infarction elicited by LAD ligature below the first branch. The impedance spectrum (1 to 1000 kHz) of normal and infarcted myocardium was measured in seven other pigs with similar infarctions. Electrical transmission of current pulses (30 microA) in infarcted tissue and in test solutions was also investigated. RESULTS: The infarct scar has a lower than normal resistivity (110 +/- 30 omega cm vs. 235 +/- 60 omega cm, p < 0.0001) and, unlike the normal myocardium, resistivity and phase angle of the scar did not change at increasing current frequencies, reflecting no capacitative response. LAD reocclusion induced a resistivity rise (510 +/- 135 omega cm, p < 0.01) and a ST segment elevation (0.6 +/- 0.7 to 9.5 +/- 5.1 mV, p = 0.002) in the ischemic peri-infarction zone, whereas the infarcted area showed ST segment elevation (0.5 +/- 0.5 to 3.8 +/- 2.6 mV, p = 0.03) with no resistivity changes. Potential decay of both ST segment and current pulses in the scar and in 0.9% NaCl solution was less than 1 mV/mm. Transmural deposition of connective tissue was seen in the center of the infarction. CONCLUSIONS: A one-month-old transmural infarction is a low resistance, noncapacitative medium that allows a good transmission of current pulses and of ST segment potential changes generated by contiguous peri-infarction ischemia.

Differential uptake of myocardial perfusion radiotracers in normal, infarcted, and acutely ischemic peri-infarction myocardium.

OBJECTIVES: We measured the uptake of technetium-99m tetrofosmin (99m Tc) and thallium-201 (201 TI) in areas of healed transmural myocardial infarction and in the regions of acute peri-infarction ischemia. METHODS: Anesthetised pigs with a 1-month old transmural infarction elicited by permanent ligature of the left anterior descending (LAD) coronary artery below the first branch underwent one hour of proximal LAD occlusion followed by injection of 99m Tc-tetrofosmin and 201TI either in the left atrium (GI, n= 19) or in the jugular vein (GII, n = 6). Twelve other pigs (GIII) with similar acute peri-infarction ischemia received 99m Tc-tetrofosmin and 201Tl into the left ventricle during cardiocirculatory arrest to rule out the effect of coronary collaterals. Radiotracer counting was determined in samples from normal, acute ischemic and necrotic regions. RESULTS: Uptake of 99m Tc-tetrofosmin and 201 Tl was greater in the infarct scar (median % of normal tissue: 20 for 99m Tc and 8.6 for 201 Tl in GI; 22 and 15 in GII) than in acute ischemic myocardium (3.2 and 2.5 in GI; 6.4 and 3.3 in GII). Radiotracer injection in arrested hearts (GIII) depicted a similar pattern (median % of injected dose: 6.2 for 99m Tc and 10 for 201Tl in the scar; 2.3 and 4.0 in acute ischemia; 2.9 and 3.5 in normal tissue). The infarcted region showed connective tissue and lack of viable myocardium. CONCLUSION: A 1-month old infarct scar with no viable myocardial tissue can take up significant fractions of 99mTc-tetrofosmin and 201Tl even in the absence of coronary collateral perfusion. Data suggest that the infarct scar can extract these radiotracers from the intraventricular blood.

Role of Vascular Disease in the Evolution of Heart Transplant Patients.

BACKGROUND: The clinical profile of heart transplantation (HT) recipients has changed in recent years. Nowadays, we have to deal with a higher number of co-morbidities, including peripheral vascular disease (PVD). Previous studies suggest an increase in post-HT morbidity and mortality associated with PVD, especially when it is symptomatic. Our study aims were to analyze the prognostic implications of the presence of PVD before transplantation and to determine the factors associated with its development after it. METHODS: HT patients (n = 217) who survived the first year after surgery were included in the study. Mean follow-up was 9 ± 5 years. RESULTS: There were no statistically significant differences in mortality rates between patients with PVD (before or after HT) and those without. One third of patients with PVD required surgery in the post-HT monitoring, either revascularization or amputation. Furthermore, the prevalence of PVD was doubled. Dyslipidemia before HT (odds ratio [OR]: 2.9, 95% confidence interval [CI]: 1.3-6.4; P < .01) and older recipient age (OR: 1.05, 95% CI: 1.01-1.09; P < .05) were independently associated with development of PVD by means of multivariate analysis. CONCLUSIONS: The presence of PVD must be evaluated individually in candidates for heart transplantation despite being a relative contraindication to it at the present time.

Peri-infarction zone at risk during the first 5 days after an acute transmural myocardial infarction: electrocardiographic evidence.

An atrial pacing test was performed daily during the initial 5 days after a first myocardial infarction (MI) in 33 patients in Killip class I or II, to assess the presence of areas at risk of ischemia. Pacing caused a transient ST-segment shift of 1 mm or more in 26 patients (79%) (positive test, Group I) in the first 3.6 +/- 1.1 days after infarction, whereas no ST-segment change developed during pacing in 7 patients (negative test, Group II). Pacing-induced electrocardiographic changes were always localized in the leads involved by the MI. Right and left ventricular filling pressures were higher in Group I than in Group II (8 +/- 4 vs 5 +/- 3 mm Hg, p less than 0.05, and 16 +/- 7 vs 12 +/- 7 mm Hg, p less than 0.02, respectively). Both groups had similar increases in peak enzyme values and a similar mortality rate (2 of 26 vs 1 of 7 at an average follow-up of 16 months). The reinfarction rate was higher in Group II (3 of 7 vs 1 of 26). In 7 patients similar to the 33 patients studied, metabolic studies revealed lactate abnormalities during pacing in 4 of the 6 patients with positive test results and unchanged metabolism in the patient with a negative test result. Thus a jeopardized peri-infarction area appears to exist in most patients soon after an uncomplicated MI. Its presence is often associated with silent heart failure, but it is probably unrelated to peak enzyme increase or to prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolonged angina pectoris and persistent negative T waves in the precordial leads: response to atrial pacing and to methoxamine-induced hypertension.

In 18 consecutive patients without a history of myocardial infarction (MI), prolonged angina pectoris with persistent negative T waves in the precordial leads was associated with a high frequency of in-hospital spontaneous angina (14 of 18, 78%), usually accompanied by S-T segment elevation, and occasionally in-hospital MI (4 of 18, 22%). Angina and MI always involved the electrocardiographic leads with negative T waves. Coronary arteriography, performed in 16 patients, revealed greater than or equal to 90% proximal diameter reduction of the left anterior descending (LAD) coronary artery in 14 patients. No patient had severe narrowing of all 3 major coronary arteries, but the 3 who had 100% LAD occlusion lacked collateral circulation. The ejection fraction was greater than or equal to 50% in 13 patients. Atrial pacing performed in 11 patients at an average rate of 142 beats/min produced a 1.0 mm S-T segment change in only 5 patients (45%), 3 of whom had an associated lactate production. Arterial systemic hypertension induced by methoxamine in 14 patients caused reversal of negative T waves without significant S-T segment shifts or chest pain and failed to elicit lactate extraction abnormalities in each of the 5 patients in whom it was determined. Thus, prolonged angina with persistent negative T waves in the precordial leads is almost invariably associated with a critical and proximal LAD obstruction, severe narrowing of 1 or 2 coronary arteries, and poor or absent collateral vessels. The relatively preserved coronary reserve in 55% of our patients suggests that negative T waves do not represent active myocardial ischemia. The study also suggests that transient "positivization" of the negative T waves may not necessarily relate to myocardial ischemia when associated with acute systemic hypertension.