Safety of low-dose spironolactone administration in chronic haemodialysis patients

Background. Prevention of cardiovascular diseases is essential in chronic haemodialysis patients. Recently, low-dose spironolactone has been shown to decrease cardiovascular mortality in patients with severe heart failure. However, since haemodialysis patients are prone to hyperkalaemia, a known side effect of spironolactone, this treatment is not used in this population. We performed a study to assess whether low-dose spironolactone (3 × 25 mg/week) could be administered without inducing hyperkalaemia in haemodialysis patients. Methods. The study design included a 2-week baseline period, followed by a 4-week treatment period in which doses of spironolactone were started at 12.5 mg three times/week for 2 weeks, then increased to 25 mg three times/week, and followed by a 2-week wash-out period. Fourteen patients receiving low-dose spironolactone after each dialysis were compared with 21 haemodialysis patients (control group). Results. Low-dose spironolactone did not change mean serum potassium (4.9 ± 0.7 vs 4.9 ± 0.3 mmol/l: control). The mean plasma canrenone level induced by administration of spironolactone 25 mg three times/week in the 14 treated patients was 13 ± 5.3 ng/ml. Serum aldosterone was not significantly modified by the administration of spironolactone in these patients [before, median 0.35; interquartile range (IQR) 0.11-2.83 nmol/l vs after, median 0.22; IQR 0.12-0.60 nmol/l, NS]. Dietary potassium intake and the use of ion-exchange resin, angiotensin-converting enzyme inhibitors and β-blockers were similar for the two groups throughout the study. Conclusion. This non-randomized and non-blinded study shows that administration of 25 mg spironolactone thrice weekly is not associated with an increased frequency of hyperkalaemia in haemodialysis patients when they are carefully monitored. More studies are required, however, before concluding that spironolactone administration is safe in the chronic haemodialysis populatio

Diagnostic value of PET-measured heterogeneity in myocardial blood flows during cold pressor testing for the identification of coronary vasomotor dysfunction

Background: We aimed to evaluate the diagnostic value of a positron emission tomography (PET)-measured heterogeneity in longitudinal myocardial blood flow (MBF) during cold pressor testing (CPT) and global MBF response to CPT from rest (ΔMBF) for identification of coronary vasomotor dysfunction. Methods and Results: In 35 patients CPT-induced alterations in epicardial luminal area were determined with quantitative angiography as the reference. MBF was assessed over the whole left ventricle as global MBF and regionally in the mid and mid-distal myocardium as MBF difference or MBF heterogeneity with nitrogen-13 ammonia and PET. The sensitivity and specificity of a longitudinal MBF difference during CPT in the identification of epicardial vasomotor dysfunction were significantly higher, than the global ΔMBF to CPT (88% vs 79% and 82% vs 64%, respectively; P<.05). Combining both parameters resulted in an optimal sensitivity of 100% at the expense of an intermediate specificity of 73%. The diagnostic accuracy was higher for the combined analysis than that for the MBF difference alone and global ΔMBF alone (91% vs 86% and 74%, respectively; P<.05). Conclusions: The combined evaluation of a CPT-induced heterogeneity in longitudinal MBF and the change in global MBF from rest may emerge as a new promising analytic approach to further optimize the identification and characterization of coronary vasomotor dysfunctio

Structural epicardial disease and microvascular function are determinants of an abnormal longitudinal myocardial blood flow difference in cardiovascular risk individuals as determined with PET/CT

Background: The aim of this study was to determine whether epicardial structural disease may affect the manifestation of a longitudinal decrease in myocardial blood flow (MBF) or MBF difference during hyperemia in cardiovascular risk individuals, and its dependency on the flow increase. Methods and Results: In 54 cardiovascular risk individuals (at risk) and in 26 healthy controls, MBF was measured with 13N-ammonia and PET/CT in mL/g/min at rest and during dipyridamole stimulation. Computed tomography coronary angiography (CTA) was performed using a 64-slice CT of a PET/CT system. Absolute MBFs during dipyridamole stimulation were mildly lower in the mid-distal than in the mid-LV myocardium in controls (2.20±.51 vs 2.29±.51, P<.0001), while it was more pronounced in at risk with normal and abnormal CTA (1.56±.42 vs 1.91±.46 and 1.18±.34 vs 1.51±.40mL/g/min, respectively, P<.0001), resulting in a longitudinal MBF difference that was highest in at risk with normal CTA, intermediate in at risk abnormal CTA, and lowest in controls (.35±.16 and .22±.09 vs .09±.04mL/g/min, respectively, P<.0001). On multivariate analysis, log-CCS and mid-LV hyperemic MBF increase, indicative of microvascular function, were independent predictors of the observed longitudinal MBF difference (P≤.004 by ANOVA). Conclusions: Epicardial structural disease and microvascular function are important determinants of an abnormal longitudinal MBF difference as determined with PET/C

Inferior vena cava parameters predict re-admission in ischaemic heart failure

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Improvement in coronary circulatory function in morbidly obese individuals after gastric bypass-induced weight loss: relation to alterations in endocannabinoids and adipocytokines

Aims To investigate the effect of surgical gastric bypass-induced weight loss and related alterations in endocannabinoids (ECs) and adipocytokine plasma levels on coronary circulatory dysfunction in morbidly obese (MOB) individuals. Methods and results Myocardial blood flow (MBF) responses to cold pressor test (CPT) from rest (ΔMBF) and during pharmacologically induced hyperaemia were measured with 13N-ammonia PET/CT in 18 MOB individuals with a body mass index (BMI) > 40 kg/m2 at baseline and after a median follow-up period of 22 months. Gastric bypass intervention decreased BMI from a median of 44.8 (inter-quartile range: 43.3, 48.2) to 30.8 (27.3, 34.7) kg/m2 (P < 0.0001). This decrease in BMI was accompanied by a marked improvement in endothelium-related ΔMBF to CPT and hyperaemic MBFs, respectively [0.34 (0.18, 0.41) from 0.03 (−0.08, 0.15) mL/g/min, P = 0.002; and 2.51 (2.17, 2.64) from 1.53 (1.39, 2.18) mL/g/min, P < 0.001]. There was an inverse correlation between decreases in plasma concentrations of the EC anandamide and improvement in ΔMBF to CPT (r = −0.59, P = 0.009), while increases in adiponectin plasma levels correlated positively with hyperaemic MBFs (r = 0.60, P = 0.050). Conversely, decreases in leptin plasma concentrations were not observed to correlate with the improvement in coronary circulatory function (r = 0.22, P = 0.400, and r = −0.31, P = 0.250). Conclusions Gastric bypass-related reduction of BMI in MOB individuals beneficially affects coronary circulatory dysfunction. The dysbalance between ECs and adipocytokines appears to be an important determinant of coronary circulatory function in obesit

Effects of SARS-COV-2 infection on outcomes in patients hospitalized for acute cardiac conditions. A prospective, multicenter cohort study (Swiss Cardiovascular SARS-CoV-2 Consortium)

BACKGROUND Although the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) causing coronavirus disease 2019 (COVID-19) primarily affects the respiratory system, the disease entity has been associated with cardiovascular complications. This study sought to assess the effect of concomitant SARS-COV-2 infection on clinical outcomes of patients hospitalized primarily for acute cardiac conditions on cardiology wards in Switzerland. METHODS In this prospective, observational study conducted in 5 Swiss cardiology centers during the COVID-19 pandemic, patients hospitalized due to acute cardiac conditions underwent a reverse-transcriptase polymerase chain reaction test at the time of admission and were categorized as SARS-COV-2 positive (cases) or negative (controls). Patients hospitalized on cardiology wards underwent treatment for the principal acute cardiac condition according to local practice. Clinical outcomes were recorded in-hospital, at 30 days, and after 1 year and compared between cases and controls. To adjust for imbalanced baseline characteristics, a subgroup of patients derived by propensity matching was analyzed. RESULTS Between March 2020 and February 2022, 538 patients were enrolled including 122 cases and 416 controls. Mean age was 68.0 ± 14.7 years, and 75% were men. Compared with controls, SARS-COV-2-positive patients more commonly presented with acute heart failure (35% vs. 17%) or major arrhythmia (31% vs. 9%), but less commonly with acute coronary syndrome (26% vs. 53%) or severe aortic stenosis (4% vs. 18%). Mortality was significantly higher in cases vs. controls in-hospital (16% vs. 1%), at 30 days (19.0% vs. 2.2%), and at 1 year (28.7% vs. 7.6%: p < 0.001 for all); this was driven primarily (up to 30 days) and exclusively (at one-year follow-up) by higher non-cardiovascular mortality, and was accompanied by a greater incidence of worsening renal function in cases vs. controls. These findings were maintained in a propensity-matched subgroup of 186 patients (93 cases and 93 controls) with balanced clinical presentation and baseline characteristics. CONCLUSIONS In this observational study of patients hospitalized for acute cardiac conditions, SARS-COV-2 infection at index hospitalization was associated with markedly higher all-cause and non-cardiovascular mortality throughout one-year follow-up. These findings highlight the need for effective, multifaceted management of both cardiac and non-cardiac morbidities and prolonged surveillance in patients with acute cardiac conditions complicated by SARS-COV-2 infection

Effects of SARS-COV-2 infection on outcomes in patients hospitalized for acute cardiac conditions. A prospective, multicenter cohort study (Swiss Cardiovascular SARS-CoV-2 Consortium).

BACKGROUND Although the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) causing coronavirus disease 2019 (COVID-19) primarily affects the respiratory system, the disease entity has been associated with cardiovascular complications. This study sought to assess the effect of concomitant SARS-COV-2 infection on clinical outcomes of patients hospitalized primarily for acute cardiac conditions on cardiology wards in Switzerland. METHODS In this prospective, observational study conducted in 5 Swiss cardiology centers during the COVID-19 pandemic, patients hospitalized due to acute cardiac conditions underwent a reverse-transcriptase polymerase chain reaction test at the time of admission and were categorized as SARS-COV-2 positive (cases) or negative (controls). Patients hospitalized on cardiology wards underwent treatment for the principal acute cardiac condition according to local practice. Clinical outcomes were recorded in-hospital, at 30 days, and after 1 year and compared between cases and controls. To adjust for imbalanced baseline characteristics, a subgroup of patients derived by propensity matching was analyzed. RESULTS Between March 2020 and February 2022, 538 patients were enrolled including 122 cases and 416 controls. Mean age was 68.0 ± 14.7 years, and 75% were men. Compared with controls, SARS-COV-2-positive patients more commonly presented with acute heart failure (35% vs. 17%) or major arrhythmia (31% vs. 9%), but less commonly with acute coronary syndrome (26% vs. 53%) or severe aortic stenosis (4% vs. 18%). Mortality was significantly higher in cases vs. controls in-hospital (16% vs. 1%), at 30 days (19.0% vs. 2.2%), and at 1 year (28.7% vs. 7.6%: p < 0.001 for all); this was driven primarily (up to 30 days) and exclusively (at one-year follow-up) by higher non-cardiovascular mortality, and was accompanied by a greater incidence of worsening renal function in cases vs. controls. These findings were maintained in a propensity-matched subgroup of 186 patients (93 cases and 93 controls) with balanced clinical presentation and baseline characteristics. CONCLUSIONS In this observational study of patients hospitalized for acute cardiac conditions, SARS-COV-2 infection at index hospitalization was associated with markedly higher all-cause and non-cardiovascular mortality throughout one-year follow-up. These findings highlight the need for effective, multifaceted management of both cardiac and non-cardiac morbidities and prolonged surveillance in patients with acute cardiac conditions complicated by SARS-COV-2 infection

GPR55 agonist lysophosphatidylinositol and lysophosphatidylcholine inhibit endothelial cell hyperpolarization via GPR-independent suppression of Na+-Ca2 + exchanger and endoplasmic reticulum Ca2 + refilling

Lysophosphatidylinositol (LPI) and lysophosphatidylcholine (LPC) are lipid signaling molecules that induce endothelium-dependent vasodilation. In addition, LPC suppresses acetylcholine (Ach)- induced responses. We aimed to determine the influence of LPC and LPI on hyperpolarizing responses in vitro and in situ endothelial cells (EC) and identify the underlying mechanisms. Using patch-clamp method, we show that LPI and LPC inhibit EC hyperpolarization to histamine and suppress Na + /Ca 2+ exchanged (NCX) currents in a concentration-dependent manner. The inhibition is non-mode-specific and unaffected by intracellular GDPβS infusion and tempol, a superoxide dismutase mimetic. In excised mouse aorta, LPI strongly inhibits the sustained and the peak endothelial hyperpolarization induced by Ach, but not by SKA-31, an opener of Ca 2+ - dependent K + channels of intermediate and small conductance. The hyperpolarizing responses to consecutive histamine applications are strongly reduced by NCX inhibition. In a Ca 2+ -re-addition protocol, bepridil, a NCX inhibitor, and KB-R7943, a blocker of reversed NCX, inhibit the hyperpolarizing responses to Ca 2+ -re-addition following Ca 2+ stores depletion. These finding indicate that LPC and LPI inhibit endothelial hyperpolarization to Ach and histamine independently of G-protein coupled receptors and superoxide anions. Reversed NCX is critical for ER Ca 2+ refilling in EC. The inhibition of NCX by LPI and LPC underlies diminished endothelium-dependent responses and endothelial dysfunction accompanied by increased levels of these lipids in the blood