Treatment-induced increase in total body potassium in patients at high risk of ventricular arrhythmias; a randomized POTCAST substudy.

OBJECTIVE: Hypokalemia is associated with increased risk of arrhythmias and it is recommended to monitor plasma potassium (p-K) regularly in at-risk patients with cardiovascular diseases. It is poorly understood if administration of potassium supplements and mineralocorticoid receptor antagonists (MRA) aimed at increasing p-K also increases intracellular potassium. METHODS: Adults aged≥18 years with an implantable cardioverter defibrillator (ICD) were randomized (1:1) to a control group or to an intervention that included guidance on potassium rich diets, potassium supplements, and MRA to increase p-K to target levels of 4.5-5.0 mmol/l for six months. Total-body-potassium (TBK) was measured by a Whole-Body-Counter along with p-K at baseline, after six weeks, and after six months. RESULTS: Fourteen patients (mean age: 59 years (standard deviation 14), 79% men) were included. Mean p-K was 3.8 mmol/l (0.2), and mean TBK was 1.50 g/kg (0.20) at baseline. After six-weeks, p-K had increased by 0.47 mmol/l (95%CI:0.14;0.81), p = 0.008 in the intervention group compared to controls, whereas no significant difference was found in TBK (44 mg/kg (-20;108), p = 0.17). After six-months, no significant difference was found in p-K as compared to baseline (0.16 mmol/l (-0.18;0.51), p = 0.36), but a significant increase in TBK of 82 mg/kg (16;148), p = 0.017 was found in the intervention group compared to controls. CONCLUSIONS: Increased potassium intake and MRAs increased TBK gradually and a significant increase was seen after six months. The differentially regulated p-K and TBK challenges current knowledge on potassium homeostasis and the time required before the full potential of p-K increasing treatment can be anticipated. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03833089).

The effect of increased plasma potassium on myocardial function; a randomized POTCAST substudy.

Plasma potassium (p-K) in the high-normal range has been suggested to reduce risk of cardiovascular arrythmias and mortality through electrophysiological and mechanical effects on the myocardium. In this study, it was to investigated if increasing p-K to high-normal levels improves systolic- and diastolic myocardial function in patients with low-normal to moderately reduced left ventricular ejection fraction (LVEF). The study included 50 patients (mean age 58 years (SD 14), 81% men), with a mean p-K 3.95 mmol/l (SD 0.19), mean LVEF 48% (SD 7), and mean Global Longitudinal Strain (GLS) -14.6% (SD 3.1) patients with LVEF 35-55% from "Targeted potassium levels to decrease arrhythmia burden in high-risk patients with cardiovascular diseases trial" (POTCAST). Patients were given standard therapy and randomized (1:1) to an intervention that included guidance on potassium-rich diets, potassium supplements, and mineralocorticoid receptor antagonists targeting high-normal p-K levels (4.5-5.0 mmol/l). Echocardiography was done at baseline and after a mean follow-up of 44 days (SD 18) and the echocardiograms were analyzed for changes in GLS, mechanical dispersion, E/A, e', and E/e'. At follow-up, mean difference in changes in p-K was 0.52 mmol/l (95%CI 0.35;0.69), P<0.001 in the intervention group compared to controls. GLS was improved with a mean difference in changes of -1.0% (-2;-0.02), P<0.05 and e' and E/e' were improved with a mean difference in changes of 0.9 cm/s (0.02;1.7), P = 0.04 and ? 1.5 (-2.9;-0.14), P = 0.03, respectively. Thus, induced increase in p-K to the high-normal range improved indices of systolic and diastolic function in patients with low-normal to moderately reduced LVEF.

Attainment of Target Antibiotic Levels by Oral Treatment of Left-Sided Infective Endocarditis: A POET Substudy.

BACKGROUND: In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs). METHODS: Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated. RESULTS: A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics. CONCLUSIONS: For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.

Potential Advances of Adjunctive Hyperbaric Oxygen Therapy in Infective Endocarditis.

Patients with infective endocarditis (IE) form a heterogeneous group by age, co-morbidities and severity ranging from stable patients to patients with life-threatening complications with need for intensive care. A large proportion need surgical intervention. In-hospital mortality is 15-20%. The concept of using hyperbaric oxygen therapy (HBOT) in other severe bacterial infections has been used for many decades supported by various preclinical and clinical studies. However, the availability and capacity of HBOT may be limited for clinical practice and we still lack well-designed studies documenting clinical efficacy. In the present review we highlight the potential beneficial aspects of adjunctive HBOT in patients with IE. Based on the pathogenesis and pathophysiological conditions of IE, we here summarize some of the important mechanisms and effects by HBOT in relation to infection and inflammation in general. In details, we elaborate on the aspects and impact of HBOT in relation to the host response, tissue hypoxia, biofilm, antibiotics and pathogens. Two preclinical (animal) studies have shown beneficial effect of HBOT in IE, but so far, no clinical study has evaluated the feasibility of HBOT in IE. New therapeutic options in IE are much needed and adjunctive HBOT might be a therapeutic option in certain IE patients to decrease morbidity and mortality and improve the long-term outcome of this severe disease.