Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases.

Cardiovascular and renal diseases are among the leading causes of death worldwide, and regardless of current efforts, there is a demanding need for therapeutic alternatives to reduce their progression to advanced stages. The stress caused by diseases leads to the activation of protective mechanisms in the cell, including chaperone proteins. The Sigma-1 receptor (Sig-1R) is a ligand-operated chaperone protein that modulates signal transduction during cellular stress processes. Sig-1R interacts with various ligands and proteins to elicit distinct cellular responses, thus, making it a potential target for pharmacological modulation. Furthermore, Sig-1R ligands activate signaling pathways that promote cardioprotection, ameliorate ischemic injury, and drive myofibroblast activation and fibrosis. The role of Sig-1R in diseases has also made it a point of interest in developing clinical trials for pain, neurodegeneration, ischemic stroke, depression in patients with heart failure, and COVID-19. Sig-1R ligands in preclinical models have significantly beneficial effects associated with improved cardiac function, ventricular remodeling, hypertrophy reduction, and, in the kidney, reduced ischemic damage. These basic discoveries could inform clinical trials for heart failure (HF), myocardial hypertrophy, acute kidney injury (AKI), and chronic kidney disease (CKD). Here, we review Sig-1R signaling pathways and the evidence of Sig-1R modulation in preclinical cardiac and renal injury models to support the potential therapeutic use of Sig-1R agonists and antagonists in these diseases.

Effects of Body Mass Index on Presentation and Outcomes of COVID-19 among Heart Transplant and Left Ventricular Assist Device Patients: A Multi-Institutional Study.

The coronavirus disease 2019 (COVID-19) pandemic continues to pose a significant threat to patients receiving advanced heart failure therapies. The current study was undertaken to better understand the relationship between obesity and outcomes of SARS-CoV-2 infection in patients with a left ventricular assist device (LVAD) or heart transplant. We performed a retrospective review of patients with a heart transplant or LVAD who presented to one of the participating 11 institutions between April 1 and November 30, 2020. Patients were grouped by body mass index (BMI) into obese (BMI ≥ 30 k/m2) and nonobese cohorts (BMI < 30 kg/m2). Multivariable logistic regression models were used to estimate effects of obesity on outcomes of interest. Across all centers, 162 heart transplant and 81 LVAD patients were identified; 54 (33%) and 38 (47%) were obese, respectively. Obese patients tended to have more symptoms at presentation. No differences in rates of hospitalization or ICU admission were noted. Obese patients with LVADs were more likely to require mechanical ventilation (39% vs. 8%, p < 0.05). No differences in renal failure or secondary infection were noted. Mortality was similar among heart transplant patients (11% [obese] vs. 16% [nonobese], p = 0.628) and LVAD patients (12% vs. 15%, p = 1.0). BMI was not associated with increased adjusted odds of mortality, ICU admission, or mechanical ventilation (all p > 0.10). In summary, acute presentations of SARS-CoV-2 among heart transplant and LVAD recipients carry a significantly higher mortality than the general population, although BMI does not appear to impact this. Further studies on the longer-term effects of COVID-19 on this population are warranted.

Comorbidities associated with risk of ICU admission in elderly patients with COVID-19: Data from academic hospital in Saudi Arabia.

The coronavirus disease 2019 (COVID-19) has affected millions of people worldwide, of which 5% required intensive care, especially mechanical ventilation. The prognosis depends on several factors including comorbidities. This study was conducted to identify the comorbidities associated with the intensive care unit (ICU) admission in elderly with COVID-19 admitted to a tertiary academic hospital. A retrospective cross-sectional study was conducted at KSUMC including all hospitalized patients (age ≥ 65 years) with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection admitted between March 2020 and August 2021. Data collection included sociodemographic characteristics, underlying comorbidities, and the Charlson comorbidity index. Comorbidities were compared between the elderly patients with COVID-19 admitted to the ICU and those not admitted to the ICU. The odds ratios were calculated and a P value of < .05 and 95% confidence intervals were used to report the statistical significance A total of 444 patients (ICU = 147, non-ICU = 297) were included in the study. The study revealed that elderly patients with COVID-19 admitted to ICU had a higher rate of mortality (n = 64, 67.4%; P < .0001) and a higher proportion of them had shortness of breath (n = 97, 38.3%; P = .007) compared to the elderly patients not admitted to ICU. The mean length of stay (P < .0001), and weight (P = .02) among ICU patients were higher than the values for the non-ICU group, while the mean oxygen saturation (SpO2; P = .006) was lower among the ICU group. The comorbidities that demonstrated a statistically significant association with ICU admission were heart failure (P = .004, odd ratio (OR) = 2.02, 95% confidence intervals (CI) [1.263, 3540]), chronic obstructive pulmonary disease (COPD; P = .027, OR = 3.361, 95% CI [1.080, 10.464]), and chronic kidney disease (P = .021, OR = 1.807, 95% CI [1.087, 3.006]). The current study identified that the comorbidities such as COPD, heart failure, and factors like SpO2 and length of stay are associated with an increased risk of ICU admission in elderly patients with COVID-19. These findings highlight the clinical implications of comorbidity among geriatric population.

The Impact of COVID-19 on Family Caregivers of Individuals With End-Stage Heart Failure.

Before the COVID-19 pandemic, family caregivers were providing a tremendous amount of care for family members with heart failure with the prevalence of caregiver reliance in heart failure expected to increase in the United States. Social distancing and other restrictions during the COVID-19 pandemic may have added further challenges to caregiving routines. The purpose of this study was to examine the family caregiver perception of the effect of COVID-19 on caregiving routines. To determine caregiver perception of COVID-19's impact, 1 Likert question and 1 open-ended response were asked. Braun and Clark's method guided open-ended response thematic analysis. The 113 replies to the open-response question yielded themes such as social isolation, added fear, anxiety, or worry, changed appointments, wearing masks, and living status change. Social isolation (41.6%) was the most common theme; the most significant theme was living status change ( P = .003), and family caregivers reported that the pandemic affected their routines either negatively or somewhat negatively (62.1%). Family caregivers are affected during times of crisis. Research and policies that recognize the residual effects of COVID-19 on caregiving practices and support care transitions for family caregivers in the heart failure population are needed.

Elucidating the Role of Cardiac Biomarkers in COVID-19: A Narrative Evaluation with Clinical Standpoints and a Pragmatic Approach for Therapeutics.

With the incidence of the unabated spreading of the COVID-19 (coronavirus disease 2019) pandemic with an increase in heart-related complications in COVID-19 patients, laboratory investigations on general health and diseases of heart have greater importance. The production of a higher level of clots in the blood in COVID-19 individuals carries a high risk of severe lethal pneumonia, pulmonary embolism, or widespread thromboembolism. The COVID-19 pandemic has raised awareness regarding the severe consequences for the cardiac system that might cause due to severe acute respiratory distress syndrome (SARS-CoV-2). COVID-19 causes acute respiratory distress syndrome (ARDS), acute myocardial infarction, venous thromboembolism, and acute heart failure in people with preexisting cardiac illness. However, as COVID-19 is primarily a respiratory infectious disease, there is still a lot of debate on whether and how cardiac biomarkers should be used in COVID-19 patients. Considering the most practical elucidation of cardiac biomarkers in COVID-19, it is important to note that recent findings on the prognostic role of cardiac biomarkers in COVID-19 patients are similar to those found in pneumonia and ARDS studies. The use of natriuretic peptides and cardiac troponin concentrations as quantitative variables should help with COVID-19/pneumonia risk classification and ensure that these biomarkers sustain their high diagnostic precision for acute myocardial infarction and heart failure. Serial assessment of D-dimers will possibly aid clinicians in the assortment of patients for venous thromboembolism imaging in addition to the increase of anticoagulation from preventive to marginally higher or even therapeutic dosages because of the central involvement of endothelitis and thromboembolism in COVID-19. Therefore, cardiac biomarkers are produced in this phase because of some pathological processes; this review will focus on major cardiac biomarkers and their significant role in COVID-19.

Changes in Acute Myocardial Infarction, Stroke, and Heart Failure Hospitalizations During COVID-19 Pandemic in Tuscany-An Interrupted Time Series Study.

Objectives: We evaluate the impact of the COVID-19 pandemic on unplanned hospitalization rates for patients without COVID-19, including their length of stay, and in-hospital mortality, overall, and for acute myocardial infarction (AMI), stroke, and heart failure in the Tuscany region of Italy. Methods: We carried out a population-based controlled interrupted time series study using segmented linear regression with an autoregressive error term based on admissions data from all public hospitals in Tuscany. The primary outcome measure was weekly hospitalization rates; secondary outcomes included length of stay, and in-hospital mortality. Results: The implementation of the pandemic-related mitigation measures and fear of infection was associated with large decreases in inpatient hospitalization rates overall (-182 [-234, -130]), unplanned hospitalization (-39 [-51, -26]), and for AMI (-1.32 [-1.98, -0.66]), stroke (-1.51 [-2.56, -0.44]), and heart failure (-8.7 [-11.1, -6.3]). Average length of stay and percent in-hospital mortality for select acute medical conditions did not change significantly. Conclusion: In Tuscany, Italy, the COVID-19 pandemic was associated with large reductions in hospitalization rates overall, as well as for heart failure, and the time sensitive conditions of AMI and stroke during the months January to July 2020.

Cardiac resynchronization therapy defibrillator: a de novo implant in a COVID-19 patient by an echo-guided axillary venous approach.

The COVID-19 pandemic has seriously revolutionized the management of patients who need an implanted cardiac implantable electronic device. We report, for the first time, a successful cardiac resynchronization therapy defibrillator implantation procedure in an 82-year-old man affected by COVID-19, recent myocardial infarction, second-degree 2:1 atrioventricular block and left bundle branch block.

What is the association of renin-angiotensin-aldosterone system inhibitors with COVID-19 outcomes: retrospective study of racially diverse patients?

OBJECTIVE: To describe the clinical outcomes of COVID-19 in a racially diverse sample from the US Southeast and examine the association of renin-angiotensin-aldosterone system (RAAS) inhibitor use with COVID-19 outcome. DESIGN, SETTING, PARTICIPANTS: This study is a retrospective cohort of 1024 patients with reverse-transcriptase PCR-confirmed COVID-19 infection, admitted to a 1242-bed teaching hospital in Alabama. Data on RAAS inhibitors use, demographics and comorbidities were extracted from hospital medical records. PRIMARY OUTCOMES: In-hospital mortality, a need of intensive care unit, respiratory failure, defined as invasive mechanical ventilation (iMV) and 90-day same-hospital readmissions. RESULTS: Among 1024 patients (mean (SD) age, 57 (18.8) years), 532 (52.0%) were African Americans, 514 (50.2%) male, 493 (48.1%) had hypertension, 365 (36%) were taking RAAS inhibitors. During index hospitalisation (median length of stay of 7 (IQR (4-15) days) 137 (13.4%) patients died; 170 (19.2%) of survivors were readmitted. RAAS inhibitor use was associated with lower in-hospital mortality (adjusted HR, 95% CI (0.56, (0.36 to 0.88), p=0.01) and no effect modification by race was observed (p for interaction=0.81). Among patients with hypertension, baseline RAAS use was associated with reduced risk of iMV, adjusted OR, 95% CI (aOR 0.58, 95% CI 0.36 to 0.95, p=0.03). Patients with heart failure were twice as likely to die from COVID-19, compared with patients without heart failure. CONCLUSIONS: In a retrospespective study of racially diverse patients, hospitalised with COVID-19, prehospitalisation use of RAAS inhibitors was associated with 40% reduction in mortality irrespective of race.

Continuous monitoring of changes in cerebral oxygenation during hemodialysis in a patient with acute congestive heart failure.

A 71-year-old man undergoing hemodialysis (HD) was admitted to our hospital with congestive heart failure (CHF) and pneumonia. After admission, ultrafiltration with HD was urgently performed because of a lack of respiratory improvement despite the use of noninvasive positive pressure ventilation. During HD, cerebral regional saturation of oxygen (rSO2) was monitored by INVOS 5100c oxygen saturation monitor (Covidien Japan, Japan) to evaluate changes in tissue oxygenation. At HD initiation, cerebral rSO2 was very low at 34% under the fraction of inspiratory oxygen (FiO2) of 0.4. Ultrafiltration was performed at the rate of 0.5 L/h thereafter, cerebral rSO2 gradually improved even as inhaling oxygen concentration decreased. At the end of HD, cerebral rSO2 improved at 40% under a FiO2 of 0.28 as excess body fluid was removed. After pneumonia and CHF improved, he was discharged. Reports of the association between cerebral oxygenation and acute CHF status in patients undergoing HD are limited; therefore, in our experience with this case, cerebral oxygenation deteriorated with the CHF status but was improved by adequate body-fluid management during HD.

Age and multimorbidities as poor prognostic factors for COVID-19 in hemodialysis: a Lebanese national study.

BACKGROUND: Hemodialysis patients with COVID-19 have been reported to be at higher risk for death than the general population. Several prognostic factors have been identified in the studies from Asian, European or American countries. This is the first national Lebanese study assessing the factors associated with SARS-CoV-2 mortality in hemodialysis patients. METHODS: This is an observational study that included all chronic hemodialysis patients in Lebanon who were tested positive for SARS-CoV-2 from 31st March to 1st November 2020. Data on demographics, comorbidities, admission to hospital and outcome were collected retrospectively from the patients' medical records. A binary logistic regression analysis was performed to assess risk factors for mortality. RESULTS: A total of 231 patients were included. Mean age was 61.46 ± 13.99 years with a sex ratio of 128 males to 103 females. Around half of the patients were diabetics, 79.2% presented with fever. A total of 115 patients were admitted to the hospital, 59% of them within the first day of diagnosis. Hypoxia was the major reason for hospitalization. Death rate was 23.8% after a median duration of 6 (IQR, 2 to 10) days. Adjusted regression analysis showed a higher risk for death among older patients (odds ratio = 1.038; 95% confidence interval: 1.013, 1.065), patients with heart failure (odds ratio = 4.42; 95% confidence interval: 2.06, 9.49), coronary artery disease (odds ratio = 3.27; 95% confidence interval: 1.69, 6.30), multimorbidities (odds ratio = 1.593; 95% confidence interval: 1.247, 2.036), fever (odds ratio = 6.66; 95% confidence interval: 1.94, 27.81), CRP above 100 mg/L (odds ratio = 4.76; 95% confidence interval: 1.48, 15.30), and pneumonia (odds ratio = 19.18; 95% confidence interval: 6.47, 56.83). CONCLUSIONS: This national study identified older age, coronary artery disease, heart failure, multimorbidities, fever and pneumonia as risk factors for death in patients with COVID-19 on chronic hemodialysis. The death rate was comparable to other countries and estimated at 23.8%.

Heart failure and COVID-19: synergism of two inflammatory conditions?

Heart failure as a comorbidity in the older population with COVID-19 poses an additional threat to those affected. Patients with both COVID-19 and heart failure share similar risk factors, which result in magnification of pathological outcomes. These include a common inflammatory pathology and related coagulopathy. Both illnesses pose a risk of arrhythmia. Polypharmacy further complicates safe drug administration and worsens the risk of medication-induced arrhythmia. Additionally, both conditions present challenges regarding attaining and maintaining an appropriate nutritional state. Exploration of the interplay between these factors demonstrates the gravity of the co-existence of these conditions and helps understand the difficulties faced when caring for this patient group. Although care provided to COVID-19 patients is primarily related to symptom presentation, based on the analysis conducted, there are some recommendations for practice in relation to evidence and guidelines when managing heart failure patients in primary care within the context of the COVID-19 pandemic.

When cardiomyopathy, cancer, and COVID-19 collide: A case report.

Malignancy has historically prohibited solid organ transplant; however, patients with effectively treated, favorable-risk cancers should not necessarily be eliminated as transplant candidates. These cases require careful review by a multidisciplinary team. Here, we report the case of a woman with end-stage heart failure undergoing heart transplant evaluation during the COVID pandemic who was found to have early-stage, hormone receptor-positive breast cancer. Given her favorable cancer-related prognosis, a multidisciplinary committee recommended lumpectomy, accelerated partial breast irradiation, and adjuvant aromatase inhibitor therapy for definitive treatment to allow for consideration of orthotopic heart transplant.

Beyond the stethoscope: managing ambulatory heart failure during the COVID-19 pandemic.

There have been nearly 70 million cases of COVID-19 worldwide, with over 1.5 million deaths at the time of this publication. This global pandemic has mandated dramatic changes in healthcare delivery with a particular focus on social distancing in order to reduce viral transmission. Heart failure patients are among the highest utilizers of health care and are at increased risk for COVID-related vulnerabilities. Effectively managing this complex and resource-intensive patient population from a distance presents new and unique challenges. Here, we review relevant data on telemedicine and remote monitoring strategies for heart failure patients and provide a framework to help providers treat this population during the COVID-19 pandemic. This includes (i) dedicated pre-visit contact and planning (i.e. confirm clinical appropriateness, presence of compatible technology, and patient comfort); (ii) utilization of virtual clinic visits (use of telehealth platforms, a video-assisted exam, self-reported vital signs, and weights); and (iii) use of existing remote heart failure monitoring sensors when applicable (CardioMEMS, Optivol, and HeartLogic). While telemedicine and remote monitoring strategies are not new, these technologies are emerging as an important tool for the effective management of heart failure patients during the COVID-19 pandemic. In general, these strategies appear to be safe; however, additional data will be needed to determine their effectiveness with respect to both process and outcomes measures.

Multi-organ damage by covid-19: congestive (cardio-pulmonary) heart failure, and blood-heart barrier leakage.

Corona virus disease-19 (covid-19) is caused by a coronavirus that is also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and is generally characterized by fever, respiratory inflammation, and multi-organ failure in susceptible hosts. One of the first things during inflammation is the response by acute phase proteins coupled with coagulation. The angiotensinogen (a substrate for hypertension) is one such acute phase protein and goes on to explain an association of covid-19 with that of angiotensin-converting enzyme-2 (ACE2, a metallopeptidase). Therefore, it is advisable to administer, and test the efficacy of specific blocker(s) of angiotensinogen such as siRNAs or antibodies to covid-19 subjects. Covid-19 activates neutrophils, macrophages, but decreases T-helper cells activity. The metalloproteinases promote the activation of these inflammatory immune cells, therefore; we surmise that doxycycline (a metalloproteinase inhibitor, and a safer antibiotic) would benefit the covid-19 subjects. Along these lines, an anti-acid has also been suggested for mitigation of the covid-19 complications. Interestingly, there are three primary vegetables (celery, carrot, and long-squash) which are alkaline in their pH-range as compared to many others. Hence, treatment with fresh juice (without any preservative) from these vegies or the antioxidants derived from purple carrot and cabbage together with appropriate anti-coagulants may also help prevent or lessen the detrimental effects of the covid-19 pathological outcomes. These suggested remedies might be included in the list of putative interventions that are currently being investigated towards mitigating the multi-organ damage by Covid-19 during the ongoing pandemic.

The soluble catalytic ectodomain of ACE2 a biomarker of cardiac remodelling: new insights for heart failure and COVID19.

The angiotensin-converting enzyme 2 (ACE2) is a type I integral membrane that was discovered two decades ago. The ACE2 exists as a transmembrane protein and as a soluble catalytic ectodomain of ACE2, also known as the soluble ACE2 that can be found in plasma and other body fluids. ACE2 regulates the local actions of the renin-angiotensin system in cardiovascular tissues, and the ACE2/Angiotensin 1-7 axis exerts protective actions in cardiovascular disease. Increasing soluble ACE2 has been associated with heart failure, cardiovascular disease, and cardiac remodelling. This is a review of the molecular structure and biochemical functions of the ACE2, as well we provided an updated on the evidence, clinical applications, and emerging potential therapies with the ACE2 in heart failure, cardiovascular disease, lung injury, and COVID-19 infection.

Determinants of healing among patients with coronavirus disease 2019: the results of the SARS-RAS study of the Italian Society of Hypertension.

OBJECTIVE: The burst of COVID-19 epidemics in Italy prompted the Italian Society of Hypertension to start an observational study to explore the characteristics of the hospitalized victims of the disease. The current analysis aimed to investigate the predictors of healing among Italian COVID-19 patients. We also assessed the effect of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers on the outcome. METHODS: We designed a cross-sectional, observational, multicenter, nationwide survey in Italy to explore the demographic and clinical characteristics of patients with confirmed COVID-19 infection. We analyzed information from 2446 charts of Italian patients admitted for certified COVID-19 in 27 hospitals. Healing from COVID-19 infection, defined as two consecutive negative swabs, was reported in 544 patients (22.2%), 95% of them were hospitalized. RESULTS: Age and Charlson Comorbidity Index were significantly lower in healing compared with nonhealing patients (63 ±â€Š15 vs. 69 ±â€Š15 and 2 ±â€Š2 vs. 3 ±â€Š2, both P < 0.05). In multivariable regression model, predictors of healing were younger age (OR: 0.99; 95% CI 0.98-0.99, P = 0.0001), absence of chronic kidney disease (OR: 0.35; 95% CI 0.17-0.70, P = 0.003) or heart failure (OR: 0.44; 95% CI, 0.28-0.70, P = 0.001). In the subgroup of patients suffering from hypertension and/or heart failure (n = 1498), no differences were observed in the use of ACE inhibitors and angiotensin receptor blockers. CONCLUSION: Our study demonstrated that younger age and absence of comorbidities play a major role in determining healing in patients with COVID-19. No effects of ACE inhibitors and angiotensin receptor blockers on the outcome was reported.

Implantation of Impella CP left ventricular assist device under the guidance of three-dimensional intracardiac echocardiography.

Impella CP is a percutaneously inserted left ventricular assist device indicated for temporary mechanical cardiac support during high risk percutaneous coronary interventions and for cardiogenic shock. The potential application of Impella has become particularly relevant during the current COVID-19 pandemic, for patients with acute severe heart failure complicating viral illness. Standard implantation of the Impella CP is performed under fluoroscopic guidance. Positioning of the Impella CP can be confirmed with transthoracic or transoesophageal echocardiography. We describe an alternative approach to guide intracardiac implantation of the Impella CP using two-dimensional and three-dimensional intracardiac echocardiography. This new technique can be useful in selected groups of patients when fluoroscopy, transthoracic and transoesophageal echocardiography is deemed inapplicable or limited for epidemiological or clinical reasons. Intracardiac three-dimensional echocardiography is a feasible alternative to the traditional techniques for implantation of an Impella CP device but careful consideration must be given to the potential limitations and complications of this technique.

A case of heart failure mimicking COVID-19 pneumonia: The role of clinical and chest computed tomography findings in the differential diagnosis.

Acute heart failure (HF) is one of the most common cardiac emergencies. Pulmonary edema caused by HF may mimic an exudative disease on chest computed tomography scans. Coronavirus disease 2019 (COVID-19) emerged in China in December 2019 and quickly spread around the world. During this pandemic period, the need to exclude the possibility of COVID-19 pneumonia in patients with acute dyspnea may cause a delay in the diagnosis and treatment of patients with acutely decompensated HF who have similar symptoms. This case report describes a diabetic patient admitted with dyspnea one week after she suffered an acute myocardial infarction. The objective of this report is to draw attention to the differential diagnosis of HF and COVID-19 pneumonia.