Calcium Antagonists Research Articles

Risk Factors, Complications and Management of Diabetes Mellitus

Diabetes mellitus can be a complex disorder described by chronic progressive metabolic disorder and chronic hyperglycemia arising from dysregulation of carbohydrate, lipid and protein metabolism. Verapamil is a class of non-dihydropyridine calcium channel blockers, which prevents the second phase of glucose stimulated insulin release by inhibiting the intake of calcium into the cytosol of beta cells and also prevents sulfonylurea and glucagon-induced insulin release. The complications of diabetes mellitus are categorized as microvascular (nephropathy, neuropathy, and retinopathy) or macrovascular (cardiovascular and cerebrovascular disease). Diabetic nephropathy is a microvascular complication described by elevated urinary albumin excretion (proteinuria) or lowered kidney glomerular filtration rate in both types of diabetic mellitus. The objective of diabetes mellitus management is to inhibit the mortality and to delay the onset of disease complications and to hinder its progression by improving patients’ blood sugar level and controlling the risk of cardiovascular disease. Metformin enhances liver, muscle & adipose tissues sensitivity to the insulin and elevate peripheral glucose utilization and also prevents gluconeogenesis and obviates glucose absorption from gastrointestinal tract.

Structural Modifications of Nimodipine Lead to Novel PDE1 Inhibitors with Anti-pulmonary Fibrosis Effects.

Our previous research demonstrated that phosphodiesterase-1 (PDE1) could work as a potential target against idiopathic pulmonary fibrosis. Nimodipine, a calcium antagonist commonly used to improve hypertension, was reported to have inhibition against PDE1. Herein, a series of nimodipine analogues were discovered as novel selective and potent PDE1 inhibitors after structural modifications. Compound 2g exhibited excellent inhibitory activity against PDE1C (IC50 = 10 nM), high selectivity over other PDEs except for PDE4, and weak calcium channel antagonistic activity. Administration of compound 2g exhibited remarkable therapeutic effects in a rat model of pulmonary fibrosis induced by bleomycin and prevented myofibroblast differentiation induced by TGF-β1. The expressions of PDE1B and PDE1C were found to be increased and concentrated in the focus of fibrosis. Compound 2g increased the levels of 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) in the lungs of rats with pulmonary fibrosis, supporting the fact that the anti-fibrosis effects of 2g were through the regulation of cAMP and cGMP.

Pharmacological Management of Hypertrophic Cardiomyopathy: From Bench to Bedside

Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is still orphan of a specific drug treatment. The erroneous consideration of HCM as a rare disease has hampered the design and conduct of large, randomized trials in the last 50 years, and most of the indications in the current guidelines are derived from small non-randomized studies, case series, or simply from the consensus of experts. Guideline-directed therapy of HCM includes non-selective drugs such as disopyramide, non-dihydropyridine calcium channel blockers, or β-adrenergic receptor blockers, mainly used in patients with symptomatic obstruction of the outflow tract. Following promising preclinical studies, several drugs acting on potential HCM-specific targets were tested in patients. Despite the huge efforts, none of these studies was able to change clinical practice for HCM patients, because tested drugs were proven to be scarcely effective or hardly tolerated in patients. However, novel compounds have been developed in recent years specifically for HCM, addressing myocardial hypercontractility and altered energetics in a direct manner, through allosteric inhibition of myosin. In this paper, we will critically review the use of different classes of drugs in HCM patients, starting from “old” established agents up to novel selective drugs that have been recently trialed in patients.

Systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy: a narrative review.

Background and ObjectiveThe prevalence of hypertrophic cardiomyopathy (HCM) is estimated to be 1 in 200 to 500 individuals, with systolic anterior motion (SAM) of the mitral valve (MV) and left ventricular outflow tract (LVOT) obstruction present in 60% to 70%. In this narrative review, we aim to elucidate the pathophysiology of SAM-septal contact and LVOT obstruction in HCM by presenting a detailed review on the anatomy of the MV apparatus in HCM, examining the various existing theories pertaining to the SAM phenomenon as supported by cardiac imaging, and providing a critical assessment of management strategies for SAM in HCM.MethodsA literature review was performed using PubMed, EMBASE, Ovid, and the Cochrane Library, of all scientific articles published through December 2021. A focus was placed on descriptive studies, reports correlating echocardiographic findings with pathologic diagnosis, and outcomes studies.Key Content and FindingsThe pathophysiology of SAM involves the complex interplay between HCM morphology, MV apparatus anatomic abnormalities, and labile hemodynamic derangements. Echocardiography and cardiac magnetic resonance (CMR) vector flow mapping have identified drag forces, as opposed to the “Venturi effect”, as the main hydraulic forces responsible for SAM. The degree of mitral regurgitation with SAM is variable, and its severity is correlated with degree of LVOT obstruction and outcomes. First line therapy for the amelioration of SAM and LVOT obstruction is medical therapy with beta-blockers, non-dihydropyridine calcium-channel blockers, and disopyramide, in conjunction with lifestyle modifications. In refractory cases septal reduction therapy is performed, which may be combined with a ‘resect-plicate-release’ procedure, anterior mitral leaflet extension, surgical edge-to-edge MV repair, anterior mitral leaflet retention plasty, or secondary chordal cutting.ConclusionsRecent scientific advances in the field of HCM have allowed for a maturation of our understanding of the SAM phenomenon. Cardiac imaging plays a critical role in its diagnosis, treatment, and surveillance, and in our ability to apply the appropriate therapeutic regimens. The increasing prevalence of HCM places an emphasis on continued basic and clinical research to further improve outcomes for this challenging population.

SERUM AND IONIZED MAGNESIUM IN ELDERLY HYPERTENSIVES

Objective: Magnesium is involved in about 600 enzymatic and metabolic reactions. In patients at risk, e.g. elderly, a magnesium deficiency has to be taken into account. This can result in a variety of diseases, e.g. cardiovascular disorder and hypertension. Diagnosis can be made by laboratory, anamnesis (drugs) or clinical symptoms. Especially elderly (up to 30 %) or hypertensives are risk patients for a magnesium deficiency. In these patients a magnesium supplementation is then often of benefit. Design and method: In our study 45 elderly hypertensives with normal renal function were investigated (serum creatinine was 1.1+/-0.1 mg/dL). All patients were older than 60 years. None of our patients took magnesium supplements. All patients had an essential hypertension grade 1 and 2 according to ESH guidelines classification. Anti-hypertensive treatment was performed using usual drugs (e.g. betablockers, calcium antagonists or Renin-Angiotensin-Aldosterone System (RAAS) blockers), no diuretics for at least 4 weeks before start of the study. Serum magnesium concentrations were measured by a Cobas Apparatus, Roche, Germany. The analysis of the measurements of ionized magnesium concentrations was carried out with a Prime Plus system from NOVA Medical Devices Corp., Rödermark, Germany. This is a point-of-care unit device with a high precision standard. The tests use either capillary blood or about 1 mL of whole blood and the complete measurement process takes about only 1 minute. Results: In serum magnesium content only 1 patient was below normal range of 1.7 md/dl. Mean+/- s.d. was 1.96+/- 0.16 mg/dl. In contrast in 12 of 45 patients ionized magnesium was significantly below the normal range (27%, 0.54+/-0.06 mmol/l). There was no correlation between serum or ionized magnesium concentrations (n.s., Pearson’ s or Spesrmann rank test, p value 0.91 and 0.41). Bood pressure was controlled. Conclusions: In conclusion normal serum magnesium values do not exclude a magnesium deficiency in elderly hypertensive patients. The determination of ionized magnesium might be a better tool in this context. A magnesium deficiency is often observed in elderly and has to be substituted in a sufficient amount to avoid cardiovascular and other diseases.

EXTREMELY HIGH DIRECT PLASMA RENIN IN A YOUNG WOMAN WITH NEGATIVE IMAGING FOR RENOVASCULAR HYPERTENSION

Objective: Direct plasma renin (DPR) has a much broader distribution than plasma renin activity (PRA). The finding in one patient of extremely high DPR values without apparent cause led us to the diagnosis and successful treatment of renovascular hypertension which had been initially ruled out by magnetic resonance angiography. Design and method: Review of the patient’s clinical records and the relevant literature. Results: A 39-year-old woman, long-term user of oral contraceptives was referred to our Hypertension Clinic. For the last two years she had presented severe hypertension, with BP often > 200/120 mmHg, poorly responding to antihypertensive drugs including ACEI or ARB plus calcium antagonists, diuretics, spironolactone, doxazosin and bisoprolol. She reported frequent holocranial non-pulsatile headaches without pallor, tachycardia, nausea or other vegetative symptoms. Laboratory testing was normal except for albuminuria (378 mg/g Cr) with normal plasma creatinine,eGFR, potassium, TSH and ACTH. Blood pressure remained high after contraceptive withdrawal. Physical examination showed only grade I overweight. ABPM showed diurnal 198/96 mmHg and nocturnal 186/89 mmHg, non-dipper without marked highs or lows. Echocardiography showed moderate LVH but ruled out heart failure. All drugs except diltiazem and doxazosin were withdrawn for a month, plasma metanephrines and cortisol suppression were normal, and plasma aldosterone was in the upper normal range (29.6 ng/dL) while DPR was extremely high (2196 mU/L, normal upper limit 39 mU/L). Renovascular hypertension (or reninoma) was suspected, but magnetic resonance renal angiography was informed as normal. However, the left kidney was significantly smaller and hypoperfused. A standard renal angiogram showed fibromuscular dysplasia with severe left stenosis. Angioplasty was performed, and after 3 months the patient’s blood pressure is well controlled with 120 mg slow-release diltiazem daily, and her plasma angiotensin and renin are normal. Conclusions: DPR can be raised by low-salt diet, hypovolemia, drugs such as diuretics, ACEIs and ARBs, hyperthyroidism, pheochromocytoma/paraganglioma and edematous states (heart or liver failure, nephrotic syndrome). However these conditions are unlikely to cause extremely high renin. Renovascular hypertension or reninoma should be suspected, even when the initial imaging seems negative. Fibromuscular dysplasia is likelier than atherosclerotic stenosis or reninoma in contraceptive users.

THE IMPACT OF HYPERTENSION AND ANTIHIPERTENSIVE TREATMENTS ON PATIENTS WITH SARS-COV-2: A RETROSPECTIVE-COHORT STUDY

Objective: Hypertension is one of the most important factors for cardiovascular disease. It has been repeatedly proposed as a prognostic factor of severe COVID-19 and has been included in clinical risk scores to predict the occurrence of critical illness in ospitalised with COVID-19. Also, it has been postulated the relation between antihypertensive drugs and the severity of COVID-19. The aims of our study were to analyze whether hypertension and antihypertensive treatment represent an independent risk factor for death or intensive care unit admission in patients with SARS-COV2. Design and method: Observational, retrospective, single-center cohort study of all patients admitted to Hospital Virgen Macarena diagnosed with COVID-19 between the months of March and December 2020. A bivariate analysis was performed using Pearson's chi-square Results: 608 patients required admission for COVID-19. A total of 83.7% were hypertensive, specifically 75.9% were under antihypertensive treatment (35.7% with only 1 drug, 29.9% were taking two drugs, 9% with three drugs, and 1.3% with 4 drugs). 26.2% were treated with an ACEI, 24.8% with ARA-II, 16.8% with calcium-antagonists, 30.9% with diuretics, 21.2% with beta-blockers, 0, 5% with alpha-blockers). Hypertension did not show a statistically significant relationship with mortality (p = 0.34), increase in mortality and ICU admissions. Neither treatment with ACEI (p = 0.4), ARB-II (p = 0.45), calcium antagonists (p = 0.53), diuretics (p = 0.68), alpha blockers (p = 0.07) demonstrated relation with those items. Surprisingly, beta-blockers increased the mortality in patients with SARS-COV2 (p = 0.048). Probably this results can be explained as these drugs were indicated for rate control in patients with atrial fibrillation (p = 0.006). The number of antihypertensive drugs used also did not show a statistically significant relationship with an increase in mortality (p = 0.978). Conclusions: Hypertension is a highly prevalent pathology in patients ospitalised with COVID-19 infection. However, high blood pressure was not associated with a higher risk for mortality in patients with SARS-COV-2, neither the type or the number of antihypertensive drug used. Only beta-blockers alter outcomes in hypertensive patients with COVID-19, as they were associated with more deaths.

NEW ONSET OF HYPERTENSION IN PATIENTS ADMITTED FOR INFECTION WITH SARS-COV-2 VIRUS

Objective: The aim of the study was to assess the clinical particularities and the lab tests in patients hospitalized for SARS-COV2 infection, with new onset of hypertension on admission. Design and method: We performed a retrospective study on 217 patients admitted to a Clinical Emergency Hospital between January 2021 and October 2021. Results: We had 217 patients admitted in internal medicine clinic for infection with SARS-COV2 virus, most of them with moderate and severe form of disease. From them, 148 patients had hypertension, 83.78% with medical history of hypertension and 16.22% with new onset of high blood pressure on admission. Patients were aged between 23 and 99 years, with an average age of 65 years. In comparison, the patients with new onset of hypertension (subgroup 1) were aged between 37 and 90 years, with an average age of 66 years. The most affected group of age was 60–69 years. In subgroup 1, the gender distribution was: 58.33% male, 41.66% female. At admission, the stages of SARS-COV2 infection in subgroup 1, according to CT examination, were severe in 52.38%, moderate 19.04%, and mild 28.57% of patients. As comorbidities in subgroup 1: cancer in 8.33%, metabolic syndrome 54.16%, dyslipidemia 4.16%, obesity 50%, type II diabetes mellitus 45.83%, chronic heart failure in 12.5% of cases (37.5% NYHA I class, 54.16% NYHA II class and 8.3% NYHA III class), atrial fibrillation in 12.5%, atherosclerosis in 16.66%, anxiety disorders in 4.16% and dementia in 8.33% of cases. High levels of inflammatory markers in Subgroup 1: CRP in 95.83%, procalcitonin in 87.5%, ferritin 79.16%, D-dimers in 83.33%, troponin 4.16%, NT-proBNP in 50% of cases. Decreased GFR was found in 65.21% of patients. Microalbuminuria was present in 29.16% of patients. The antihypertensive medication during hospitalization was: diuretics in 45.83%% of cases, betablockers in 33.34%, calcium blockers in 8.33%, angiotensin converting enzyme inhibitors in 16.67%. Conclusions: Hypertension with new onset during SARS-COV2 infection and its persistence in post-covid syndrome may have complex pathogenic mechanisms and require personalized therapeutic decision.

TRENDS IN ANTIHYPERTENSIVE MEDICATION USE AFTER ISCHEMIC STROKE (1999–2020)

Objective: Hypertension (HT) is a major risk factor for stroke. The guidelines for the management of HT in stroke patients have been updated periodically and changed. We aimed to examine trends in antihypertensive medications use after ischemic stroke Design and method: Retrospective study on ischemic stroke patients discharged from 3 tertiary general hospitals, during the periods: 1999–2001, 2014–16 and 2019–2020. Data analysis was performed using SPSS statistical software (IBM SPSS Statistics 24; Chicago, IL, USA). Results: We included 1,806 patients, 753 (41.6%) women, mean age 69.7 (± 10) years. Comparing the periods, the patients are now older (68.7–69.9–71.3; p = 0.003) and have a higher frequency of HT (67.3% vs. 73.8% vs. 75.4%; p = 0.0001). HT was the most prevalent vascular risk factor in all periods. At discharge, more antihypertensive drugs were used progressively (in 56.4% vs 69.1% vs 84.7% of patients; p = 0.0001). There was a clear increase in the number of antihypertensive drugs used (mean 0.94 ± 0.8 vs 1.6 ± 1.05 vs 2.1 ± 0.5 drugs; p = 0.0001). Use of diuretics (14%-41.1%-63.8%; p = 0.0001), angiotensin-converting enzyme inhibitors (37.1%-43.8%-54%; p = 0.0001), and angiotensin receptor blockers (12.3%-24.3%-31.1%; p = 0.0001) increased progressively. On the contrary, use of calcium antagonists decreased (25%-22.5%-15.1%; p = 0.0001) Conclusions: The last 20 years has seen a significant increase in antihypertension medication use after ischemic stroke. At present, antihypertensive drugs are one of the most important medications in these patients.

PROFIL PERESEPAN OBAT HIPERTENSI PADA PASIEN RAWAT JALAN DI PUSKESMAS BETOAMBARI PERIODE JANUARI – JUNI TAHUN 2020 DI KOTA BAUBAU

Hypertension or high blood pressure is a condition in which blood vessels have persistently elevated pressure. This research method is done by collecting data in the form of secondary data. Secondary data was obtained from the Pharmacy section to find out the data on the number of patient visits. The data taken in the form of age group, gender, type of drug, drug class and drug combination. The results showed that the number of prescriptions obtained from January to June was 174 prescriptions and the highest percentage of drug use in hypertension patients based on gender was 115 prescriptions (66.91%) women, namely in the age group 50 years, 96 prescriptions were used. (83.47%), the use of drugs based on Hypertension drugs that was most widely prescribed was Amlodipine with 144 prescriptions (78.68%), the most prescribed group of Hypertension drugs was Calcium Antagonists with 144 (83.75%) prescriptions The most combined drugs were Amlodipine + Captopril with 18 prescriptions (58.06%)

Renin-Angiotensin-Aldosterone System (RAS) Inhibitors May Suppress the Prevalence of Peripheral Arterial Disease (PAD) in Elderly, Chronic Hemodialysis Patients.

According to the hypertension guidelines, calcium antagonists are recommended as antihypertensive drugs for Stage 5 of chronic kidney disease (CKDG5) and late elderly patients, whereas renin-angiotensin-aldosterone system (RAS) inhibitors (RASi) are not recommended. We screened elderly CKDG5D patients at a single outpatient maintenance hemodialysis center for the progression of peripheral arterial disease (PAD) using the ankle-brachial index (ABI) and skin perfusion pressure (SPP) tests, as well as logistic regression analysis, to determine the association between PAD and the treatment with RASi and the association between the treatment with RASi and the need for hospitalization within one year of observation. With the presence of PAD as the explanatory variable and the presence of RASi as the objective variable, the odds ratio was 1.23 (95% confidence interval [CI] 0.37 to 3.82) in univariate analysis. After adjusting for confounding factors (age, gender, and hypertension), the odds ratio in multivariate analysis was 0.83 (95% CI 0.46 to 6.08). The presence or absence of PAD was significantly associated with an odds ratio of 3.24 (p = .04, 95% CI 1.0 to 10.25) and 4.63 (p = .026, 95% CI 1.20 to 17.84) in univariate and multivariate analyses, respectively, when the outcome was hospitalization at one year, regardless of the presence or absence of RASi. However, in univariate analysis, the odds ratio was 1.23 (95% CI 0.37 to 3.82) with RASi status as the explanatory variable and one-year hospitalization as the objective variable. After adjusting for confounders, the odds ratio in multivariate analysis was 0.83 (95% CI 0.46 to 6.08). Although further large-scale, multicenter studies are needed to establish the evidence, our results suggest that RASi treatment may have a suppressive effect on the prevalence of PAD and the need for hospitalization in elderly CKDG5 dialysis (CKDG5D) patients.

Changes in antihypertensive treatment in surviving patients SARS-CoV-2 respiratory infection and its cardiovascular impact after one year of follow-up

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The management of antihypertensive drugs and especially ACEI/ARA2 during the first wave of the SARS-CoV-2 pandemic was a matter of debate. The change in antihypertensive treatment during the pandemic and its repercussions have not been sufficiently studied. Methods Observational and prospective study that analyzed consecutive patients admitted for respiratory infection and positive polymerase chain reaction (PCR) between March 1 and April 30, 2020. During the period analyzed, 921 patients were registered, of whom 673 patients were discharged; among them 359 were patients with a diagnosis of arterial hypertension and pharmacological treatment. These patients were followed up in days, from the time of discharge to data analysis, with a mean of 352±70.4 days. Results The mean age was 74.4±12.9 years, and 50.7% were male. A total of 28.7% were diabetic patients, 49% were dyslipidemic, 17.8% were smokers, and 19.8% were obese. Of the patients analyzed, 13.4% had a previous diagnosis of ischemic heart disease, a similar percentage, 13.1% had heart failure, and 13.6% had atrial fibrillation. The antihypertensive drugs analyzed were ACE inhibitors (angiotensin-converting enzyme inhibitors), ARA-2 (angiotensin II receptor antagonists), calcium antagonists, thiazide diuretics, loop diuretics, aldosterone antagonists, beta-blockers and alpha-blockers. At discharge, 75.8% of the patients maintained their antihypertensive treatment, and the remaining 24.2% were modified. Prior to admission, 77.2% were taking ACE inhibitors or ARA-2; however, in 16.4% of the patients they were discontinued after admission. In contrast, treatment with calcium antagonists increased from 27.6% to 34.1% after hospitalization. In both cases there were statistically significant differences in the bivariate analysis in the McNemar test (p < 0.05 in both cases), with no differences in the other antihypertensive drugs analyzed. After follow-up, the combined event occurred in 28 patients, with the most frequent event being the development of HF; in contrast, only 0.8% presented ACS. Overall mortality was 8.9%. Picture 1 shows the events recorded according to the change in antihypertensive treatment and the maintenance or discontinuation of ACEI/ARA-2 in those patients who were already taking it on admission. Similarly, a survival analysis was performed in which no differences were observed in terms of all-cause mortality or major cardiovascular events between patients who maintained their antihypertensive treatment and those who modified it. Conclusions In the population surviving SARS-CoV-2 respiratory infection, maintaining or discontinuing treatment with ACEI/ARA-2 did not influence mortality or the appearance of major cardiovascular events after the first year of follow-up.

MO165: The Controversial Role of Proteinuria and Urinary Output After Radical Nephrectomy in the Development Of Acute Kidney Injury: Double Agents

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) is increasingly common and associated with adverse short- and long-term outcomes in oncological patients who require radical nephrectomy (RN) for the presence of renal cancer. As defined by the KDIGO Criteria classification system, the diagnosis of AKI is nowadays based on changes in the serum creatinine levels (sCr) or urine output. However, these parameters often underestimate the severity of renal damage and therefore recent insights have resulted in the implementation of proteinuria as means of more accurately assessing for AKI. Proteinuria represents indeed an indicator of both glomerular and renal endothelial injury in chronic disease (CKD), whereas in AKI the presence of proteinuria could be derived from a tubular dysfunction. In the RN scenario, it is still debatable if the development of a mild to severe proteinuria after surgery could be considered a marker of renal damage resulting in AKI or, on the opposite, could be a physiological sign of adaptive compensatory hyperfiltration promoted by the remanent counterlateral kidney. The aim of our study was to investigate if the development of a postoperative proteinuria plays a positive or negative role in the prevention of AKI in a consecutive cohort of nephrectomized patients affected by renal cancer. METHOD We enrolled a consecutive cohort of 131 patients who underwent RN due to the presence of a kidney mass suspected of malignancy from 2018 to 2021 in a tertiary care urological Institution. The following data were considered: age, gender, body mass index (BMI), smoke, TNM staging, Fuhrman grading, hypertension, diabetes, cardiovascular events, dyslipidaemia, medical therapy (ACE-inhibitors (ACEi), angiotensin II receptor blockers (ARBs), calcium antagonists, beta blockers and diuretics), proteinuria in 24 h, urine volume in 24 h, preoperative haematocrit and haemoglobin. Serum creatinine (s-Cr) values [Kinetic Picrate standardized (COBAS C 800) for IDMS] were collected before surgery (t 0) and at 24, 48 and 72 h after surgery and at dismissal (respectively t 1, t 2 and tf) to detect renal function fluctuations and the subsequent risk of AKI. GFR was estimated at baseline using CKD-EPI 2012 and MDRD formula. The level of proteinuria was measured at 24 h postoperative and was standardized on the urine volume. Each operated patient underwent the same pre-peri- and postoperative medical protocol in terms of surgical and anesthesiologic management. Patients affected by pre-existing medical nephropathies with proteinuria were excluded. Comparisons between groups were performed using the Kruskal–Wallis rank sum test for numerical variables and Pearson's Chi-squared test for categorical variables. Logistic regression was used to identify variables odds ratio for AKI onset after surgery. RESULTS Descriptive analysis is shown in Table 1. Our analysis surprisingly underlined that 66% of overall patients experienced AKI after surgery. Moreover, the analysis showed a significant difference (P value < .05) between the AKI cohort and the non-AKI group concerning basal serum creatinine (sCr), eGFR using both CKD-EPI and MDRD and postoperative urine volume. In particular, the lower the basal sCr or eGFR, the higher was the risk of developing AKI. Concerning the urine output, the median volume of AKI population was significantly less in respect to their counterpart, but far from the critical definition of oliguria or anuria (Table 1 and Figure 1). On the contrary, no evidence related to a possible prognostic role of proteinuria was underlined. CONCLUSION Our work underlined that proteinuria does not represent a valid biomarker for AKI development after RN. On the contrary, basal eGFR, serum creatinine and postoperative urinary volume could be promising tools to predict and follow the acute renal damage after RN.

MO466: Impact of Renal Insufficiency on Choice of Rhythm or Rate Control in Atrial Fibrillation and Subsequent Effects on Cardiovascular and Mortality Outcomes

Abstract BACKGROUND AND AIMS Atrial fibrillation remains the most common sustained arrhythmia in the general population, with prevalence inversely correlated with renal function. Management of atrial fibrillation relies on either rhythm control or rate control, however, the choice of treatment in patients with impaired renal function remains contentious. Accordingly, we examined clinical practice and subsequent treatment outcomes. METHOD Based on nationwide healthcare registers, all patients with atrial fibrillation were identified in Denmark between 2000 and 2021. Patients aged < 18 years, and with previous prescriptions on amiodarone, digoxin, beta-blockers, calcium antagonists, or anti-coagulative medicine, or without a pre-existent record of creatinine level were excluded. Patients were stratified into two groups receiving either rhythm or rate control with the expulsion of patients with no treatment. Baseline renal function was calculated using the CKD-EPI equation based on recent plasma creatinine. The probability of rhythm control versus rate control stratified on estimated glomerular filtration rate (eGFR) (>90mL/min/1.73m2, 60–90 mL/min/1.73m2, 30–60 mL/min/1.73m2, <30 mL/min/1.73m2) was estimated using odds ratios based on multiple logistic regression with a subsequent appraisal of the risk of cardiovascular outcomes and death based on the Aalen–Johansen and Kaplan–Meier estimators, respectively and multiple Cox regression. RESULTS A total of 37 920 patients were included. Rate control (n = 34 315) was associated with even gender distribution (female gender 50.1%), mean age 74.5 (SD ± 11.8) years and median eGFR 75.9 (IQR 59.9–87.8 mL/min/1.73m2). Rhythm control (n = 3605) was associated with predominantly male gender (66.4%), a mean age of 68.5 (SD ± 12.1) and median eGFR 81.2 (IQR 66.4–91.6 mL/min/1.73m2). eGFR-stratified odds ratios for rhythm control versus rate control were 0.91 (95% CI 0.84–1.0) for eGFR 60–90 mL/min/1.73m2, 0.85 (0.75–0.96) for eGFR 30–60 mL/min/1.73m2 and 0.77 (0.61–0.98) for eGFR < 30 mL/min/1.73m2 compared to patients with eGFR > 90 mL/min/1.73m2 . With rate control as reference, adjusted hazard ratios for subsequent cardiovascular outcomes were 1.51 (95% CI 1.40–1.62) for eGFR > 90 mL/min/1.73m2, 1.53 (1.45–1.62) for eGFR 60–90 mL/min/1.73m2, 1.86 (1.68–2.05) for eGFR 30–60 mL/min/1.73m2 and 1.88 (1.47–2.41) for eGFR < 30 mL/min/1.73 m2. Cumulative risks of cardiovascular outcomes are shown in Figure 1. Adjusted hazard ratios for subsequent all-cause mortality, with rate control as reference, were 1.19 (95% CI 0.95–1.5) for eGFR > 90 mL/min/1.73m2, 1.11 (0.96–1.29) for eGFR 60–90 mL/min/1.73m2, 1.25 (1.05–1.55) for eGFR 30–60 mL/min/1.73m2 and 1.66 (1.08–2.54) for eGFR < 30 mL/min/1.73 m2. Survival curves are shown in Figure 2. CONCLUSION Rhythm control was less likely employed and was associated with a progressively increased risk of cardiovascular and mortality outcomes in patients with renal insufficiency as compared to rate control; thus, supporting contemporary clinical practice where the choice of rate control appears to prevail.

Study of effect of nimodipine and acetaminophen on postictal symptoms in depressed patients after electroconvulsive therapy (SYNAPSE)

BackgroundPostictal phenomena as delirium, headache, nausea, myalgia, and anterograde and retrograde amnesia are common manifestations after seizures induced by electroconvulsive therapy (ECT). Comparable postictal phenomena also contribute to the burden of patients with epilepsy. The pathophysiology of postictal phenomena is poorly understood and effective treatments are not available. Recently, seizure-induced cyclooxygenase (COX)-mediated postictal vasoconstriction, accompanied by cerebral hypoperfusion and hypoxia, has been identified as a candidate mechanism in experimentally induced seizures in rats. Vasodilatory treatment with acetaminophen or calcium antagonists reduced postictal hypoxia and postictal symptoms. The aim of this clinical trial is to study the effects of acetaminophen and nimodipine on postictal phenomena after ECT-induced seizures in patients suffering major depressive disorder. We hypothesize that (1) acetaminophen and nimodipine will reduce postictal electroencephalographic (EEG) phenomena, (2) acetaminophen and nimodipine will reduce magnetic resonance imaging (MRI) measures of postictal cerebral hypoperfusion, (3) acetaminophen and nimodipine will reduce clinical postictal phenomena, and (4) postictal phenomena will correlate with measures of postictal hypoperfusion.MethodsWe propose a prospective, three-condition cross-over design trial with randomized condition allocation, open-label treatment, and blinded end-point evaluation (PROBE design). Thirty-three patients (age > 17 years) suffering from a depressive episode treated with ECT will be included. Randomly and alternately, single doses of nimodipine (60 mg), acetaminophen (1000 mg), or water will be given two hours prior to each ECT session with a maximum of twelve sessions per patient. The primary outcome measure is ‘postictal EEG recovery time’, expressed and quantified as an adapted version of the temporal brain symmetry index, yielding a time constant for the duration of the postictal state on EEG. Secondary outcome measures include postictal cerebral perfusion, measured by arterial spin labelling MRI, and the postictal clinical ‘time to orientation’.DiscussionWith this clinical trial, we will systematically study postictal EEG, MRI and clinical phenomena after ECT-induced seizures and will test the effects of vasodilatory treatment intending to reduce postictal symptoms. If an effect is established, this will provide a novel treatment of postictal symptoms in ECT patients. Ultimately, these findings may be generalized to patients with epilepsy.Trial registrationInclusion in SYNAPSE started in December 2019. Prospective trial registration number is NCT04028596 on the international clinical trial register on July 22, 2019.

Relationship Between Resting Heart Rate and Microalbuminuria in Adults With Hypertension: National Health and Nutrition Examination Survey 2009-2018.

BackgroundThe impact of elevated resting heart rate on early-stage renal dysfunction, manifesting as microalbuminuria, in hypertension is unclear. This study aimed to analyze the association between resting heart rate and microalbuminuria in patients with hypertension according to their blood pressure status. In addition, the effect of antihypertensive agents on this relationship was evaluated.Methods and ResultsWe searched the National Health and Nutrition Examination Survey for eligible participants from 2009 to 2018. Data on key parameters such as age, sex, blood pressure, heart rate, albumin creatinine ratio, and medication were collected for analysis. Subsequently, participants were classified according to the heart rate quartile and blood pressure status for subgroups assessment. A total of 5,692 participants were enrolled in this study. After adjusting the confounding factors, there was a linear association between resting heart rate and microalbuminuria in patients with hypertension (OR 1.184 [per 1 SD]; 95% CI: 1.101, 1.274; P < 0.001). However, the association between elevated resting heart rate and microalbuminuria was not significant in patients with uncontrolled hypertension (OR 1.092 [per 1 SD]; 95% CI: 0.935, 1.275; P = 0.269). The OR of the indirect effect of β-blockers on the risk of microalbuminuria incidence through heart rate was 0.926 (95% CI: 0.895, 0.956), while the direct effect was 1.374 (95% CI: 1.138, 1.662, P = 0.010). Similarly, dihydropyridine calcium channel blockers were associated with a higher prevalence of microalbuminuria (OR 1.300, 95% CI: 1.058, 1.597, P = 0.013), but the association between non-dihydropyridine calcium channel blockers and microalbuminuria was not significant (OR 1.207, 95% CI: 0.737, 1.978, P = 0.454).ConclusionElevated resting heart rate is associated with a high risk of microalbuminuria in untreated patients and patients with controlled hypertension. Although there is a linear association between heart rate and microalbuminuria, the use of β-blockers exhibits a significantly increase in the prevalence of microalbuminuria in hypertension. Likewise, dihydropyridine calcium channel blockers may increase the risk of microalbuminuria in hypertension.

Elevated resting heart rate as independent in-hospital prognostic marker in COVID-19.

BackgroundScarce and non-homogeneous data are available on the prognostic value of clinic heart rate (HR) in coronavirus disease 2019 (COVID-19).MethodsThe present study evaluated in 389 patients hospitalized for COVID-19 the in-hospital prognostic value of resting HR, assessed over different time periods, i.e., at hospital admission, during initial 3 days and 7 days of hospitalization.ResultsResults show that assessment of this hemodynamic variable during hospitalization provides information on the clinical outcome of the patients, greater HR values being associated with a worse in-hospital prognosis. The prognostic value of elevated HR during COVID-19: 1) was independent on other confounders such as age, gender, comorbidities and fever, 2) appeared to be strengthened by repeated measurements of HR during the initial 3/7 days of hospitalization, and 3) was detectable in patients in which the therapeutic intervention did not include drugs, such as beta-blockers, calcium antagonists, digoxin, ivabradine and antiarrhythmic compounds known to interfere with HR.ConclusionsHeart rate may represent an important marker of a patient’s outcome in COVID-19.

Simultaneous Quantitation of Clevidipine and Its Active Metabolite H152/81 in Human Whole Blood by LC-MS/MS: Application to Bioequivalence Study.

Clevidipine is an ultrashort-acting dihydropyridine calcium antagonist, which can control blood pressure accurately. It is necessary to develop a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method to quantitate clevidipine and its active metabolite H152/81 for clinical pharmacokinetic study and therapeutic drug monitoring. Liquid–liquid extraction was used for sample preparation, and clevidipine-d7 and H152/81-13C-d3 were chosen as the isotope internal standard. The chromatographic separation was performed on an ACE Excel 2 Phenyl column (50 × 2.1 mm). Mass quantification was carried out on the multiple reaction monitoring of the transitions of m/z 473.1→338.1, 480.1→338.1, 356.0→324.0, and 362.2→326.2 for clevidipine, clevidipine-d7, H152/81, and H152/81-13C-d3. The validated method gave an excellent linearity over a concentration range of 0.1–30 ng/ml for clevidipine and 2–600 ng/ml for H152/81. Other fully validated content such as accuracy, precision, extraction recovery, matrix effect, and stability were also investigated and showed satisfactory results. It was strongly recommended that whole blood is the first choice for clinical bioanalysis. Using whole blood for sample analysis can reduce the whole blood collection volume (1 ml vs. 4 ml) and shorten the time from sample collection to storage to 5 min, and there is no centrifugation process and precooling in the ice water bath, which can further reduce the instability caused by exposure. The method was successfully applied to a bioequivalence study of clevidipine butyrate-injectable emulsion.

Acute management of atrial fibrillation in congestive heart failure with reduced ejection fraction in the emergency department

IntroductionAcute heart rate control for atrial fibrillation (AF) with rapid ventricular response (RVR) in the emergency department (ED) is often achieved utilizing intravenous (IV) non-dihydropyridine calcium channel blockers (CCB) or beta blockers (BB). For patients with concomitant heart failure with a reduced ejection fraction (HFrEF), the American Heart Association and other clinical groups note that CCB should be avoided due to their potential negative inotropic effects. However, minimal evidence exists to guide this current recommendation. The primary objective of this study was to compare the incidence of adverse effects in the HFrEF patient population whose AF with RVR was treated with IV diltiazem or metoprolol in the ED. MethodsThis single center, retrospective review included patients ≥18 years old with HFrEF who presented in AF with RVR and received IV diltiazem or metoprolol in the ED. The primary outcome was adverse effects of therapy defined as: 1) hypotension (systolic blood pressure < 90 mmHg requiring fluid bolus or vasopressors) or bradycardia (heart rate < 60 beats/min) within 60 min of medication administration 2) worsening heart failure symptoms defined as increased oxygen requirements within four hours or inotropic support within 48 h. Secondary outcomes included the incidence of rate control failure, patient disposition, ED length of stay, hospital length of stay, and in-hospital mortality. ResultsOne hundred and twenty-five patients met inclusion criteria, with 57 receiving diltiazem and 68 receiving metoprolol. Overall adverse effects for diltiazem and metoprolol were similar (32% vs. 21%, P = 0.217). However, there was a significantly higher incidence of worsening heart failure symptoms within the diltiazem group (33% vs 15%, P = 0.019). Rate control failure at 60 min did not differ significantly between diltiazem and metoprolol (51% vs 62%, P = 0.277). ConclusionsIn HFrEF patients with AF, there was no difference in total adverse events in patients treated with IV diltiazem compared to metoprolol. However, the diltiazem group had a higher incidence of worsening CHF symptoms defined as increased oxygen requirement within four hours or initiation of inotropic support within 48 h.

Association of Antihypertensives and Cognitive Impairment in Long-Term Care Residents.

Certain classes of antihypertensive medication may have different associations with cognitive impairment. To examine the association between prevalent use of antihypertensive medications that stimulate (thiazides, dihydropyridine calcium channel blockers, angiotensin type I receptor blockers) versus inhibit (angiotensin-converting enzyme inhibitors, beta-blockers, non-dihydropyridine calcium channel blockers) type 2 and 4 angiotensin II receptors on cognitive impairment among older adults residing in Veterans Affairs (VA) nursing homes for long-term care. Retrospective cohort study. Long-term care residents aged 65 + years admitted to a VA nursing home from 2012 to 2019 using blood pressure medication and without cognitive impairment at admission. Main exposure was prevalent use of angiotensin II receptor type 2 and 4-'stimulating' (N = 589), 'inhibiting' (N = 3,219), or 'mixed' (N = 1,715) antihypertensive medication regimens at admission. Primary outcome was any cognitive impairment (Cognitive Function Scale). Over an average of 5.4 months of follow-up, prevalent use of regimens containing exclusively 'stimulating' antihypertensives was associated with a lower risk of any incident cognitive impairment as compared to prevalent use of regimens containing exclusively 'inhibiting' antihypertensives (HR 0.83, 95% CI 0.74-0.93). Results for the comparison between 'mixed' versus 'inhibiting' regimens were in the same direction but not statistically significant (HR 0.96, 95% CI 0.88-1.06). For residents without cognitive impairment at baseline, prevalent users of regimens containing exclusively antihypertensives that stimulate type 2 and 4 angiotensin II receptors had lower rates of cognitive impairment as compared to prevalent users of regimens containing exclusively antihypertensives that inhibit these receptors. Residual confounding cannot be ruled out.