Benefit of natriuresis and cardiac resynchronisation therapy in acute decompensated heart failure with cardiorenal syndrome and hypernatraemia.

A man in his eighties with acute heart failure and cardiorenal syndrome developed severe hypernatraemia with diuresis. In this situation, palliation is often considered when renal replacement therapy is inappropriate. The literature to guide treatment of dysnatraemia in this setting is limited. Diuretics often worsen hypernatraemia and fluid replacement exacerbates heart failure. We describe a successful approach to this clinical Catch-22: sequential nephron blockade with intravenous 5% dextrose. Seemingly counterintuitive, the natriuretic effect of this combination had not previously been compared with diuretic monotherapy for heart failure. Yet this immediately effective strategy generated a high natriuresis-to-diuresis ratio and functioned as a bridge to cardiac resynchronisation therapy (CRT). In conjunction with a low salt diet, CRT facilitated the maintenance of sodium homeostasis and fluid balance. Thus, by improving the underlying pathophysiology (ie, inadequate cardiac output), CRT may enhance the outcomes of patients with cardiorenal syndrome and hypernatraemia.

Cardiovascular therapy use, modification, and in-hospital death in patients with COVID-19: A cohort study.

AIMS: To assess the associations of exposure and modifications in exposure (i.e., discontinuation on admission, initiation during hospitalization) to eight common cardiovascular therapies with the risk of in-hospital death among inpatients with coronavirus disease 2019 (COVID-19). METHODS: In this observational study including 838 hospitalized unvaccinated adult patients with confirmed COVID-19, the use of cardiovascular therapies was assessed using logistic regression models adjusted for potential confounders. RESULTS: No cardiovascular therapy used before hospitalization was associated with an increased risk of in-hospital death. During hospitalization, the use of diuretics (aOR 2.59 [1.68-3.98]) was associated with an increase, and the use of agents acting on the renin-angiotensin system (aOR 0.39 [0.23-0.64]) and lipid-lowering agents (aOR 0.41 [0.24-0.68]) was associated with a reduction in the odds of in-hospital death. Exposure modifications associated with decreased survival were the discontinuation of an agent acting on the renin-angiotensin system (aOR 4.42 [2.08-9.37]), a ß-blocker (aOR 5.44 [1.16-25.46]), a lipid-modifying agent (aOR 3.26 [1.42-7.50]) or an anticoagulant (aOR 5.85 [1.25-27.27]), as well as the initiation of a diuretic (aOR 5.19 [2.98-9.03]) or an antiarrhythmic (aOR 6.62 [2.07-21.15]). Exposure modification associated with improved survival was the initiation of an agent acting on the renin-angiotensin system (aOR 0.17 [0.03-0.82]). CONCLUSION: In hospitalized and unvaccinated patients with COVID-19, there was no detrimental association of the prehospital use of any regular cardiovascular medication with in-hospital death, and these therapies should be continued as recommended.

Impact of the COVID-19 pandemic on cardiovascular heart disease medication use: time-series analysis of England's prescription data during the COVID-19 pandemic (January 2019 to October 2020).

BACKGROUND: Management of high blood pressure (BP) typically requires adherence to medication regimes. However, it is known that the COVID-19 pandemic both interrupted access to some routine prescriptions and changed some patient health behaviours. AIM: This study, therefore, retrospectively investigated prescription reimbursement of cardiovascular (CVD) medicines as a proxy measure for patient adherence and access to medicines during the pandemic. METHODS: A cohort study of all primary care patients in England prescribed CVD medicines. The exposure was to the global pandemic. Prescriptions were compared before and after the pandemic's onset. Statistical variation was the outcome of interest. RESULTS: Descriptive statistics show changes to monthly prescriptions, with wide confidence intervals indicating varying underlying practice. Analysis of variance reveals statistically significant differences for bendroflumethiazide, potassium-sparing diuretics, nicorandil, ezetimibe, ivabradine, ranolazine, colesevelam and midodrine. After the pandemic began (March-October 2020), negative parameters are observed for ACE inhibitors, beta-blockers, calcium channel blockers, statins, antiplatelet, antithrombotics, ARBs, loop diuretics, doxazosin, bendroflumethiazide, nitrates and indapamide, indicating decelerating monthly prescription items (statistically significant declines of calcium channel blockers, antithrombotic, adrenoreceptor blockers and diuretics) of CVD medicines within the general population. Many data points are not statistically significant, but fluctuations remain clinically important for the large population of patients taking these medications. CONCLUSION: A concerning decline in uptake of CVD therapies for chronic heart disease was observed. Accessible screening and treatment alongside financial relief on prescription levies are needed. A video abstract is (4 min 51 s) available: https://bit.ly/39gvEHi.

Association of renin-angiotensin-aldosterone system inhibition with Covid-19 hospitalization and all-cause mortality in the UK biobank.

AIMS: With growing evidence on the protective effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in coronavirus disease 2019 (Covid-19), we aimed to thoroughly investigate the association between the use of major classes of antihypertensive medications and Covid-19 outcomes in comparison with the use of ACEIs and ARBs. METHODS: We conducted a population-based study in patients with pre-existing hypertension in the UK Biobank with data from the first 2 SARS-CoV-2 waves prior population-based vaccination. Multivariable logistic regression analysis was performed adjusting for a wide range of confounders. RESULTS: The use of either ß-blockers (BBs), calcium-channel blockers (CCBs) or diuretics was associated with a higher risk of Covid-19 hospitalization compared to ACEI use (adjusted OR (95%CI): 1.66 [1.43-1.93]) and ARB use (1.53 [1.30-1.81]). The risk of 28-day mortality among Covid-19 patients was also increased among users of BBs, CCBs or diuretics when compared to ACEI users (1.74 [1.30-2.33]) but not when compared to ARB users (1.26 [0.93-1.71]). The association between BB, CCB or diuretic use (compared to ACEI use) and 28-day mortality among hospitalized Covid-19 patients narrowly missed statistical significance (1.47 [0.99-2.18]) but it was statistically significant when the analysis was restricted to patients hospitalized during the second SARS-CoV-2 wave (1.80 [1.15-2.83]). CONCLUSION: Our results suggest protective effects of inhibition of the renin-angiotensin-aldosterone system on Covid-19 hospitalization and mortality, particularly with ACEI, among patients with pharmaceutically treated hypertension. If confirmed by randomized controlled trials, this finding could have high clinical relevance for treating hypertension during the SARS-CoV-2 pandemic.

[Tactics of antihypertensive therapy during COVID-19 pandemic].

Results of foreign and Russian studies indicate a higher mortality rate of patients with concomitant cardiovascular diseases (CVD) due to the new coronavirus infection COVID-19. It has been proven that arterial hypertension, as one of the significant risk factors for the development of concomitant cardiovascular diseases, is associated with a more severe prognosis of COVID-19. This article presents the results of modern studies and large meta-analyzes of necessity and safety of the use of blockers of the renin-angiotensin-aldosterone system in patients with arterial hypertension and COVID-19. The data of studies show that an angiotensin-converting enzyme inhibitor (ACE inhibitor) and a thiazide-like diuretic is a pathogenetically rational combination. It realizes various ways of lowering blood pressure by reducing the activity of the renin-angiotensin-aldosterone system, which is achieved by using an ACE inhibitor, and natriuresis due to diuretics. As an example, a highly effective fixed combination of drugs is considered, characterized by good tolerance, which consists of an ACE inhibitor lisinopril and a thiazide-like diuretic indapamide of prolonged action. The authors expressed the opinion that the appointment of the fixed combination drug Diroton Plus (Gedeon Richter) will contribute to effective control of blood pressure and organoprotection in conditions of increased thrombogenic and prooxidative potential, characteristic of COVID-19 both in the acute stage and within the post-COVID Syndrome.

Drug-drug interactions between treatment specific pharmacotherapy and concomitant medication in patients with COVID-19 in the first wave in Spain.

Primary aim was to assess prevalence and severity of potential and real drug-drug interactions (DDIs) among therapies for COVID-19 and concomitant medications in hospitalized patients with confirmed SARS-CoV-2 infection. The secondary aim was to analyze factors associated with rDDIs. An observational single center cohort study conducted at a tertiary hospital in Spain from March 1st to April 30th. rDDIs refer to interaction with concomitant drugs prescribed during hospital stay whereas potential DDIs (pDDIs) refer to those with domiciliary medication. DDIs checked with The University of Liverpool resource. Concomitant medications were categorized according to the Anatomical Therapeutic Chemical classification system. Binomial logistic regression was carried out to identify factors associated with rDDIs. A total of 174 patients were analyzed. DDIs were detected in 152 patients (87.4%) with a total of 417 rDDIs between COVID19-related drugs and involved hospital concomitant medication (60 different drugs) while pDDIs were detected in 105 patients (72.9%) with a total of 553 pDDIs. From all 417 rDDIs, 43.2% (n = 180) were associated with lopinavir/ritonavir and 52.9% (n = 221) with hydroxychloroquine, both of them the most prescribed (106 and 165 patients, respectively). The main mechanism of interaction observed was QTc prolongation. Clinically relevant rDDIs were identified among 81.1% (n = 338) ('potential interactions') and 14.6% (n = 61) (contraindicated) of the patients. Charlson index (OR 1.34, 95% IC 1.02-1.76) and number of drugs prescribed during admission (OR 1.42, 95% IC 1.12-1.81) were independently associated with rDDIs. Prevalence of patients with real and pDDIs was high, especially those clinically relevant. Both comorbidities and polypharmacy were found as risk factors independently associated with DDIs development.

Severe acute respiratory syndrome coronavirus-2- or pregnancy-related cardiomyopathy, a differential to be considered in the current pandemic: a case report.

BACKGROUND: There are limited data on cardiovascular complications of coronavirus disease 2019 in pregnancy, and there are only a few case reports on coronavirus disease 2019 related cardiomyopathy in pregnancy. Differentiation between postpartum cardiomyopathy and coronavirus disease 2019 related cardiomyopathy in pregnant women who develop severe acute respiratory syndrome coronavirus-2 infection during peripartum could be challenging. Here, we present a case of possible coronavirus disease 2019 related cardiomyopathy in a pregnant patient, followed by a discussion of potential differential diagnosis. CASE PRESENTATION: In this case report, we present the case of a young pregnant Iranian woman who developed heart failure with pulmonary edema after cesarean section. She was treated because of low left ventricular ejection fraction and impression of postpartum cardiomyopathy, and her severe dyspnea improved by intravenous furosemide. On day 3, she exhibited no orthopnea or leg edema, but she was complaining of severe and dry cough. Further evaluation showed severe acute respiratory syndrome coronavirus-2 infection. CONCLUSIONS: The possibility of severe acute respiratory syndrome coronavirus-2 infection should be considered in any pregnant woman who develops cardiomyopathy and pulmonary edema.

SARS-CoV-2 infection in an infant with severe dilated cardiomyopathy.

A four- and a half-month-old girl with severe dilated cardiomyopathy due to neonatal enterovirus myocarditis, treated with diuretics and milrinone for the past 4 months, was infected with SARS-CoV-2. The disease course was characterised by high fever and gastrointestinal symptoms. Cardiac function, as measured by echocardiography, remained stable. The treatment focused on maintaining a normal heart rate and a stable fluid balance. In children with severe underlying cardiac disease, even a mild SARS-CoV-2 infection can require close monitoring and compound treatment.

Two cases of coronavirus 2019-related cardiomyopathy in pregnancy.

At our institution, 2 of the initial 7 pregnant patients with confirmed coronavirus disease 2019 severe infection (28.6%; 95% CI, 8.2%-64.1%) developed cardiac dysfunction with moderately reduced left ventricular ejection fractions of 40%-45% and hypokinesis. Viral myocarditis and cardiomyopathy have also been reported in nonpregnant coronavirus disease 2019 patients. A case series of nonpregnant patients with coronavirus disease 2019 found that 33% of those in intensive care developed cardiomyopathy. More data are needed to ascertain the incidence of cardiomyopathy from coronavirus disease 2019 in pregnancy, in all pregnant women with coronavirus disease 2019, and those with severe disease (eg, pneumonia). We suggest an echocardiogram in pregnant women with coronavirus disease 2019 pneumonia, in particular those necessitating oxygen, or those who are critically ill, and we recommend the use of handheld, point-of-care devices where possible to minimize contamination of staff and traditional large echocardiogram machines.

Heart failure with preserved ejection fraction in coronavirus disease 2019 patients: the promising role of diuretic therapy in critically ill patients.

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on diastolic function is less known. We describe a 46-year-old man with a history of mild hypertension who presented to the emergency department with fever, cough, and myalgia for 2 days. The patient was tested positive for SARS-CoV-2. He was admitted and started on a combination of antiviral and antimicrobial therapy. He developed respiratory distress 2 days later, and O2 saturation declined. Blood tests showed an increased N-terminal pro-B type natriuretic peptide (NT-proBNP) level, and echocardiography showed normal left ventricular ejection fraction and E/e' ratio of 16. Computed tomography scan showed interstitial pulmonary oedema and prominent peripheral pulmonary vascular markings. Given these findings, heart failure with preserved ejection fraction (HFpEF) was considered. Low-dose diuretic was started, and fluid administration was restricted, resulting in a decrease in NT-proBNP level, clinical and haemodynamic stabilization, and improved oxygenation. This case highlights the occurrence of HFpEF in coronavirus disease 2019.

The Association of COVID-19 With Acute Kidney Injury Independent of Severity of Illness: A Multicenter Cohort Study.

RATIONALE & OBJECTIVE: Although coronavirus disease 2019 (COVID-19) has been associated with acute kidney injury (AKI), it is unclear whether this association is independent of traditional risk factors such as hypotension, nephrotoxin exposure, and inflammation. We tested the independent association of COVID-19 with AKI. STUDY DESIGN: Multicenter, observational, cohort study. SETTING & PARTICIPANTS: Patients admitted to 1 of 6 hospitals within the Yale New Haven Health System between March 10, 2020, and August 31, 2020, with results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing via polymerase chain reaction of a nasopharyngeal sample. EXPOSURE: Positive test for SARS-CoV-2. OUTCOME: AKI by KDIGO (Kidney Disease: Improving Global Outcomes) criteria. ANALYTICAL APPROACH: Evaluated the association of COVID-19 with AKI after controlling for time-invariant factors at admission (eg, demographic characteristics, comorbidities) and time-varying factors updated continuously during hospitalization (eg, vital signs, medications, laboratory results, respiratory failure) using time-updated Cox proportional hazard models. RESULTS: Of the 22,122 patients hospitalized, 2,600 tested positive and 19,522 tested negative for SARS-CoV-2. Compared with patients who tested negative, patients with COVID-19 had more AKI (30.6% vs 18.2%; absolute risk difference, 12.5% [95% CI, 10.6%-14.3%]) and dialysis-requiring AKI (8.5% vs 3.6%) and lower rates of recovery from AKI (58% vs 69.8%). Compared with patients without COVID-19, patients with COVID-19 had higher inflammatory marker levels (C-reactive protein, ferritin) and greater use of vasopressors and diuretic agents. Compared with patients without COVID-19, patients with COVID-19 had a higher rate of AKI in univariable analysis (hazard ratio, 1.84 [95% CI, 1.73-1.95]). In a fully adjusted model controlling for demographic variables, comorbidities, vital signs, medications, and laboratory results, COVID-19 remained associated with a high rate of AKI (adjusted hazard ratio, 1.40 [95% CI, 1.29-1.53]). LIMITATIONS: Possibility of residual confounding. CONCLUSIONS: COVID-19 is associated with high rates of AKI not fully explained by adjustment for known risk factors. This suggests the presence of mechanisms of AKI not accounted for in this analysis, which may include a direct effect of COVID-19 on the kidney or other unmeasured mediators. Future studies should evaluate the possible unique pathways by which COVID-19 may cause AKI.

Lack of association of antihypertensive drugs with the risk and severity of COVID-19: A meta-analysis.

BACKGROUND: The association of antihypertensive drugs with the risk and severity of COVID-19 remains unknown. METHODS AND RESULTS: We systematically searched PubMed, MEDLINE, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and medRxiv for publications before July 13, 2020. Cohort studies and case-control studies that contain information on the association of antihypertensive agents including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium-channel blockers (CCBs), ß-blockers, and diuretics with the risk and severity of COVID-19 were selected. The random or fixed-effects models were used to pool the odds ratio (OR) with 95% confidence interval (CI) for the outcomes. The literature search yielded 53 studies that satisfied our inclusion criteria, which comprised 39 cohort studies and 14 case-control studies. These studies included a total of 2,100,587 participants. We observed no association between prior usage of antihypertensive medications including ACEIs/ARBs, CCBs, ß-blockers, or diuretics and the risk and severity of COVID-19. Additionally, when only hypertensive patients were included, the severity and mortality were lower with prior usage of ACEIs/ARBs (overall OR of 0.81, 95% CI 0.66-0.99, p < 0.05 and overall OR of 0.77, 95% CI 0.66-0.91, p < 0.01). CONCLUSIONS: Taken together, usage of antihypertensive drugs is not associated with the risk and severity of COVID-19. Based on the current available literature, it is not recommended to abstain from the usage of these drugs in COVID-19 patients. REGISTRATION: The meta-analysis was registered on OSF (https://osf.io/ynd5g).

[Diabetes and COVID-19: analysis of the clinical outcomes according to the data of the russian diabetes registry].

BACKGROUND: Data on the national level and worldwide show a higher rate of mortality in patients with diabetes mellitus (DM) due to COVID-19, which determines the high relevance of risk factor analysis for outcomes in DM patients to substantiate the strategy for this category of patients. AIM: To assess the effect of clinical and demographic parameters (age, gender, body mass index (BMI), glycemic control (HbA1c), and antidiabetic and antihypertensive drugs, including ACE inhibitors and ARBs) on clinical outcomes (recovery or death) in patients with type 2 DM. MATERIALS AND METHODS: A retrospective analysis of the Russian Register of Diabetes database was performed, including patients with type 2 DM (n=309) who suffered pneumonia/COVID-19 in the period from 01.02.2020 to 27.04.2020 and the indicated outcome of the disease (recovery or death) RESULTS: The percentage of lethality was determined to be 15.2% (47 of 309 people). The degree of lethality was found to be significantly higher in males (OR=2.08; 95% CI 1.1–3.9; p=0.022) and in patients on insulin therapy (OR=2.67; 95% CI; 1.42–5.02; p=0.002), while it was significantly lower in patients with an age <65 years (OR=0.34; 95% CI 0.18–0.67; p=0.001) and in patients receiving metformin (OR=0.26; 95% CI 0.14–0,5; p<0.0001), antihypertensive therapy (OR=0.43; 95% CI 0.22–0.82; p=0.009), β-blockers (OR=0.26; 95% CI 0.08–0.86; p=0.018), diuretics (OR=0.4; 95% CI 0.17–0.93; p=0.028) and renin-angiotensin system blockers (ACE inhibitors or ARBs) (OR=0.36; 95% CI 0.18–0.74; p=0.004). A tendency to an increase in lethality at higher rates of HbA1c and BMI was present, but it did not reach a statistical significance. Differences between patients receiving insulin therapy and those who were not receiving the insulin therapy were observed as follows: a significantly longer duration of type 2 DM (13.4 vs. 6.8 years, respectively; p<0.0001), worse overall glyacemic control (HbA1c: 8.1% vs. 7.0%, resp.; p<0.0001), and three times more frequent failure to achieve the HbA1c goal by more than 2.5% (14.7% vs. 5.9%, resp.; p=0.04). CONCLUSION: The identified risk factors for lethality in patients with type 2 DM indicate that good glycemic control and previous treatment with metformin and antihypertensive drugs (including RAS blockers) could reduce the frequency of deaths. In patients on insulin therapy, a higher lethality degree was associated with worse glycemic control.

Slow Recovery from Critical Coronavirus Disease 2019 Pneumonia in an Immunosuppressed Renal Transplant Recipient with Early Acute Cardiorenal Syndrome.

With the global spread of SARS-Cov-2 infections, increasing numbers of COVID-19 cases have been reported in transplant recipients. However, reports are lacking concerning the treatment and prognosis of COVID-19 pneumonia in renal transplant recipients with acute cardiorenal syndrome. We report here the complete clinical course of a renal transplant recipient with critical COVID-19 pneumonia. In the early phase of SARS-Cov-2 infection, the patient exhibited extensive lung lesions and significant acute kidney and heart injuries, which required treatment in the ICU. After correcting the arrhythmia and heart failure, the patient recovered quickly from the acute kidney injury with a treatment of intensive diuresis and strict control of fluid intake. Without cessation of oral immunosuppressive agents, the patient presented a delayed and low antibody response against SARS-Cov-2 and reappeared positive for the virus twice after being discharged. Nevertheless, the patient's pneumonia continued to improve and he fully recovered in 69 days. This effectively treated case may be meaningful and referable for the treatment of COVID-19 pneumonia in other transplant recipients with acute cardiorenal syndrome.

COVID-19 in patients with heart failure: the new and the old epidemic.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread in nearly 200 countries in less than 4 months since its first identification; accordingly, the coronavirus disease 2019 (COVID 2019) has affirmed itself as a clinical challenge. The prevalence of pre-existing cardiovascular diseases in patients with COVID19 is high and this dreadful combination dictates poor prognosis along with the higher risk of intensive care mortality. In the setting of chronic heart failure, SARS-CoV-2 can be responsible for myocardial injury and acute decompensation through various mechanisms. Given the clinical and epidemiological complexity of COVID-19, patiens with heart failure may require particular care since the viral infection has been identified, considering an adequate re-evaluation of medical therapy and a careful monitoring during ventilation.

Use of distinct anti-hypertensive drugs and risk for COVID-19 among hypertensive people: A population-based cohort study in Southern Catalonia, Spain.

The use of some anti-hypertensive drugs in the current COVID-19 pandemic has become controversial. This study investigated possible relationships between anti-hypertensive medications use and COVID-19 infection risk in the ambulatory hypertensive population. This is a population-based retrospective cohort study involving 34 936 hypertensive adults >50 years in Tarragona (Southern Catalonia, Spain) who were retrospectively followed through pandemic period (from 01/03/2020 to 30/04/2020). Two data sets including demographic/clinical characteristics (comorbidities and cardiovascular medications use) and laboratory PCR codes for COVID-19 were linked to construct an anonymized research database. Cox regression was used to calculate multivariable hazard ratios (HRs) and estimate the risk of suffering COVID-19 infection. Across study period, 205 PCR-confirmed COVID-19 cases were observed, which means an overall incidence of 586.8 cases per 100 000 persons-period. In multivariable analyses, only age (HR: 1.03; 95% CI: 1.02-1.05; P < .001) and nursing home residence (HR: 19.60; 95% CI: 13.80-27.84; P < .001) appeared significantly associated with increased risk of COVID-19. Considering anti-hypertensive drugs, receiving diuretics (HR: 1.22; 95% CI: 0.90-1.67; P = .205), calcium channel blockers (HR: 1.29; 95%CI: 0.91-1.82; P = .148), beta-blockers (HR: 0.97; 95% CI: 0.68-1.37; P = .844), and angiotensin-converting enzyme inhibitors (HR: 0.83; 95% CI: 0.61-1.13; P = .238) did not significantly alter the risk of PCR-confirmed COVID-19, whereas receiving angiotensin II receptor blockers was associated with an almost statistically significant reduction risk (HR: 0.67; 95% CI: 0.44-1.01; P = .054). In conclusion, our data support that receiving renin-angiotensin-aldosterone system inhibitors does not predispose for suffering COVID-19 infection in ambulatory hypertensive people. Conversely, receiving angiotensin II receptor blockers could be related with a reduced risk.