Summary
It has been proposed that modest changes in plasma potassium can alter the tendency towards cardiac arrhythmias. If this were so, patients with coronary artery disease might be especially susceptible. Thus, myocardial electrical excitability was measured in patients with mild essential hypertension and known coronary artery disease after 8 weeks of treatment with a potassium-conserving diuretic (amiloride) and a similar period on a potassium-losing diuretic (chlorthalidone) in a randomised study. Plasma potassium concentrations were on average 1 mmol/L lower during the chlorthalidone phase compared to amiloride therapy. Blood pressure and volume states as assessed by bodyweight, plasma renin and noradrenaline (norepinephrine) concentrations were similar on the 2 regimens. Compared to amiloride treatment, the chlorthalidone phase was associated with an increased frequency of ventricular ectopic beats (24-hour Holter monitoring) and a higher Lown grading, increased upslope and duration of the monophasic action potential, prolonged ventricular effective refractory period, and increased electrical instability during programmed ventricular stimulation.
The above results indicate that because potassium-losing diuretic therapy can increase myocardial electrical excitability in patients with ischaemic heart disease, even minor falls in plasma potassium concentrations are probably best avoided in such patients.
Résumé
On a avancé que des changements modestes du potassium plasmatique peuvent aggraver la tendance aux arythmies cardiaques. Si cela est exact, les malades porteurs de maladie des artères coronaires devraient être spécialement sensibles à ce risque. On a donc mesuré l’excitabilité myocardique chez des malades ayant une discrète hypertension essentielle et une maladie artérielle coronaire connue, après 8 semaines d’un traitement par un diurétique d’épargne du potassium (amiloride) et après une période égale de traitement par un diurétique éliminateur du potassium (chlorthalidone) au cours d’une étude randomisée. Les concentrations plasmatiques du potassium ont été en moyenne 1 mmol/l plus basses pendant le traitement par chlorthalidone par rapport à celles mesurées pendant le traitement par amiloride. La pression sanguine, les concentrations plasmatiques de rénine et d’adrénaline ont été comparables dans les deux cas ainsi que les volumes si l’on en juge par les poids corporels. Comparée au traitement par amiloride, la période chlorthalidone a été associée à une augmentation de la fréquence des battements ventriculaires ectopiques (enregistrement Holter de 24 heures) et à une classification de Lown plus élevée, une augmentation de la pente ascendante et de la durée du potentiel d’action monophasique, une prolongation de la période réfractaire effective ventriculaire et une augmentation de l’instabilité électrique pendant la stimulation ventriculaire programmée.
Ces résultats indiquent que, étant donné qu’un traitement diurétique par un éliminateur du potassium peut augmenter l’excitabilité électrique du myocarde chez les malades porteurs d’une maladie ischémique, il vaut mieux chez de tels malades éviter une diminution des concentrations plasmatiques de potassium, fussent-elles mineures.
Zusammenfassung
Es wurde behauptet, daβ geringe Veränderungen beim Plasma-Kalium die Tendenz zu kardialen Arrhythmien verändern kann. Wenn dies so ist, können Patienten mit Koronararterien-Krankheit besonders empfindlich sein. Die myokardiale elektrische Erregbarkeit wurde daher bei Patienten mit leichter essentieller Hypertonie und bekannter Koronararterien-Erkrankung nach einer 8-wöchigen Therapie mit einem Kalium-sparenden Diuretikum (Amilorid) und nach einem ähnlichen Zeitraum mit einem Kalium-verlierenden Diuretikum (Chlorthalidon) in einer randomisierten Studie gemessen. Die Kalium-Konzentrationen im Plasma waren im Durchschnitt 1 mmol/L niedriger während der Phase mit Chlorthalidon als bei der Amilorid-Therapie. Blutdruck und der durch das Körpergewicht bestimmte Volumenstatus, Plasmarenin und die Noradrenalin (Norepinephrin) —Konzentration waren unter beiden Behandlungen ähnlich. Im Vergleich zu der Behandlung mit Amilorid erfolgte während der Chlorthalidon-Phase eine erhöhte Frequenz von ventrikulären ektopischen Schlägen (24-Stunden Holter-Monitoring) und höhere Lown-Grade, verlängerte Dauer des monophasischen Aktionspotentials, verlängerte ventrikuläre effektive Refraktoritätsperiode und eine erhöhte elektrische Instabilität während der programmierten ventrikulären Stimulation.
Die genannten Ergebnisse weisen darauf hin, daβ selbst geringere Senkungen der Plasmakonzentrationen des Kaliums bei solchen Patienten wahrscheinlich am besten vermieden werden sollten, weil eine Kalium-verlierende diuretische Therapie die myokardiale elektrische Erregbarkeit bei Patienten mit ischämischer Herzkrankheit erhöhen kann.
Resumen
Se ha pensado que modificaciones moderadas del potasio plasmático pueden alterar la tendencia a las arritmias cardiacas. Si así fuera, serían especialmente susceptibles los pacientes de cardiopatía coronaria. En consecuencia, se ha medido la excitabilidad eléctrica miocárdica en casos de hipertensión esencial leve y arteriopatía coronaria conocida después de 8 semanas de tratamiento con un diurético conservador de potasio (amiloride) y de un período análogo de toma de un diurético perdedor del elemento (clortalidona) en un estudio aleatorizado. Las concentraciones de potasio plasmático fueron por término medio de 1 mmol/l menores durante la fase de clortalidona que con la terapéutica basada en amiloride. La presión arterial y los estados de volumen estimados por el peso corporal y las concentraciones de renina y noradrenalina (norepinefrina) plasmáticas fueron semejantes en los dos regímenes. Comparado con el tratamiento con amiloride, lafase clortalidona supuso un incremento en la frecuencia de latidos ventriculares ectópicos (vigilancia Holter de 24 horas) y en la graduacion de Lown, era mayor pendiente hacia arribay una mayor duración delpotencial de acción monofásico, un período refractario efectivo ventricular prolongado y una mayor inestabilidad eléctrica durante la estimulación ventricular prolongada.
Estos resultados indican que por efecto de la terapéutica diurética perdedora de potasio puede aumentar la excitabilidad eléctrica miocárdica en los pacientes de cardiopatía isquémica, por lo que en estos enfermos probablemente lo mejor es evitar incluso los menores descensos de las concentraciones de potasio plasmático.
Resumo
Considerou-se que mudanças modestas na concentração de potássio no plasma poderiam alterar a tendência a se contrat arritmias cardíacas, o que tornaria os pacientes portadores de doença artero-coronariana especialmente suscetíveis. Assim sendo, a excitabilidade elétrica do miocârdio foi medida nos pacientes portadores de hipertensão essencial leve, bem como de doenças artero-coronarianas estabelecidas, após 8 semanas de tratamento com um diurético poupador de potássio (amilorida) e um período comparável com um diurético liberador de potássio (clortalidona). As concentrões de potássio no plasma foram em média de 1 mmol/L mais baixas durante a fase da clortalidona que durante a terapia com amilorida. A pressão sanguínea e os estados de volume conforme determinados pelo peso corporal, bem como as concentrções de noradrenalina (norepinefrina) e de renina no plasma foram semelhantes nos dois regimes. Se comparada ao tratamento com amilorida, a fase com clortalidona foi associada a uma maior frequência de batidas ectópicas do ventrículo (controle de Holter sobre 24 horas), bem como a uma classificação de Lown mais baixa, a um aumento da subida e da duração do potencial monofásico de ação, um período refratário efetivo prolongado do ventrículo e a uma maior instabilidade elétrica durante a estimulação programada do ventrículo.
Tais resultados indicam que mesmo pequenas reduções nas concentrações de potássio no plasma devem ser absolutamente evitadas em tais pacientes, uma vez que uma terapia com diurético liberador de potássio pode aumentar a excitabilidade elétrica do miocárdio em pacientes com doença cardiaca isquêmica.
Riassunto
E stato suggerito che modeste variazioni del potassio plasmatico possono favorire l’insorgenza di aritmie cardiache. Se così fosse, pazienti con malattia coronarica dovrebbero essere particolarmente suscettibili. Pertanto, l’eccitabilità elettrica miocardica fu misurata in uno studio randomizzato in pazienti con ipertensione arteriosa lieve e malattia coronarica nota dopo 8 settimane di trattamento con un diuretico risparmiatore di potassio (amiloride) e un analogo periodo con un diuretico potassio disperdente (clortalidone). La concentrazione plasmatica di potassio fu in media inferiore di 1 mmol/l durante il periodo con clortalidone rispetto al periodo con amiloride. La pressione arteriosa e lo stato di idratazione valutato con il peso corporeo, l’attività reninica plasmatica e la concentrazione di noradrenalina (norepinefrina) furono simili con i due trattamenti. Rispetto alla amiloride, il periodo con clortalidone risultò associato ad aumetata frequenza di extrasistoli ventricolari (monitoraggio sec. Holter), e ad un più alto indice di Lown,ad un aumento della pendenza e della durata del Potenziale d’azione monofasico, ad un aumento del periodo refrattario effettivo ventricolare e ad un aumento dell’instabilità elettrica in corso di stimolazione ventricolare programmata. I risultati sopra riportati indicano che, poichè i diuretici potassio-disperdenti possono aumentare l’eccitabilità elettrica miocardica in pazienti con cardiopatia ischemica, in tali pazienti è probabilmente meglio evitare anche una ipopotassiemia di modesta entità.
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Ikram, H., Espiner, E.A. & Nicholls, M.G. Diuretics, Potassium and Arrhythmias in Hypertensive Coronary Disease. Drugs 31 (Suppl 4), 101–108 (1986). https://doi.org/10.2165/00003495-198600314-00012
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DOI: https://doi.org/10.2165/00003495-198600314-00012