Impact of the COVID-19 Pandemic on Elective and Emergency Inpatient Procedure Volumes in Switzerland - A Retrospective Study Based on Insurance Claims Data.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) pandemic forced hospitals to redistribute resources for the treatment of patients with coronavirus disease 2019 (COVID-19), yet the impact on elective and emergency inpatient procedure volumes is unclear. METHODS: We analyzed anonymized data on 234 921 hospitalizations in 2017-2020 (55.9% elective) from a big Swiss health insurer. We used linear regression models to predict, based on pre-pandemic data, the expected weekly numbers of procedures in 2020 in the absence of a pandemic and compared these to the observed numbers in 2020. Compensation effects were investigated by discretely integrating the difference between the two numbers over time. RESULTS: During the first COVID-19 wave in spring 2020, elective procedure numbers decreased by 52.9% (95% confidence interval -64.5% to -42.5%), with cardiovascular and orthopedic elective procedure numbers specifically decreasing by 45.5% and 72.4%. Elective procedure numbers normalized during summer with some compensation of postponed procedures, leaving a deficit of -9.9% (-15.8% to -4.5%) for the whole year 2020. Emergency procedure numbers also decreased by 17.1% (-23.7% to -9.8%) during the first wave, but over the whole year 2020, net emergency procedure volumes were similar to control years. CONCLUSION: Inpatient procedure volumes in Switzerland decreased considerably in the beginning of the pandemic but recovered quickly after the first wave. Still, there was a net deficit in procedures at the end of the year. Health system leaders must work to ensure that adequate access to non-COVID-19 related care is maintained during future pandemic phases in order to prevent negative health consequences.

[Myocardial Infarction in an Athlete]. / Myokardinfarkt bei einem Sportler.

Myocardial Infarction in an Athlete Abstract. We report the case of a male athlete with a myocardial infarction caused by intracoronary thrombus formation, which was associated with prior cannabis consumption. Cannabis is a rare cause of myocardial infarction and is poorly recognized as a cardiovascular risk factor. Because of the ongoing process of marijuana legalization in many countries, there is concern about an increasing number of cannabis-related myocardial infarctions especially in young patients. Several pathophysiological mechanisms have been proposed and warrant further investigation.

Chronic Coronary Syndromes in Women: Challenges in Diagnosis and Management.

Sex matters in science. This particularly applies to ischemic heart disease, which displays key differences in pathophysiology, presentation, and effectiveness in diagnostic strategies and management between women and men. However, underrepresentation of women in randomized trials has led to an evidence gap in clinical practice. Nevertheless, it has become clear that women present with a higher burden of symptoms and comorbidities, experience worse outcomes, but are less likely to have flow-limiting stenosis in epicardial coronary arteries than men. A major contributor to this paradox is coronary microvascular disease, a heterogeneous disorder with multifactorial etiology that predominantly affects women. There is a significant interplay between coronary microvascular disease, obstructive coronary artery disease, and the cardiovascular risk associated with it, with impaired vasomotor function often preceding the development of advanced atheroma. This novel concept has recently been referred to as chronic coronary syndromes, which better meets the female phenotype of ischemic heart disease, questioning current management recommendations that still largely apply to flow-limiting stenoses in epicardial coronary arteries typically found in men. The goal of this review is to highlight the most recent scientific advances in understanding chronic coronary syndromes in women. It provides practical advice with focus on challenges in diagnosis and management, and discusses perspectives towards the implementation of sex-specific, safer, and more effective therapeutic strategies.

Inferior control of low-density lipoprotein cholesterol in women is the primary sex difference in modifiable cardiovascular risk: A large-scale, cross-sectional study in primary care.

BACKGROUND AND AIMS: Sex differences in cardiovascular prevention have been reported, yet the role of sex with regard to different modifiable risk factors such as low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (BP), and glycated hemoglobin (HbA1c) in primary care settings is unclear. Therefore, we studied sex differences in assessment and measured values of LDL-C, BP, and HbA1c in primary and secondary cardiovascular prevention delivered by general practitioners. METHODS: This cross-sectional study was based on electronic medical records of 59,092 primary care patients (51.9% women) aged 40-79 years in Switzerland. Multilevel regression was used to model associations of sex with assessment and measured values of LDL-C, BP, and HbA1c in 2018. RESULTS: In both primary and secondary prevention, women had lower LDL-C assessment rates (age-adjusted odds ratio (aOR) 0.71 [95% confidence interval (CI) 0.67 to 0.75] and 0.70 [CI 0.51 to 0.95]), and higher measured LDL-C values than men (age-adjusted difference 0.30 mmol/L [CI 0.25 to 0.35] and 0.28 mmol/L [CI 0.07 to 0.48]). Compared with men, women in primary prevention displayed lower BP and HbA1c assessment frequencies (aOR 0.77 [CI 0.73 to 0.81] and 0.76 [CI 0.71 to 0.80]) and measured values (age-adjusted difference -2.49 mmHg [CI -2.99 to -1.79] and -0.19% [CI -0.24 to -0.14]), while there was no sex difference in secondary prevention. Age-dependent increases in measured values of LDL-C, BP, and HbA1c were greater in women than men. CONCLUSIONS: Control of LDL-C in women in primary care should be improved to reduce sex-based inequalities in prevention of cardiovascular disease.

Efficacy and Safety of Abbreviated Eptifibatide Treatment in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

The glycoprotein IIb/IIIa inhibitor eptifibatide, administered as bolus followed by infusion, is an adjunctive antithrombotic treatment during primary percutaneous coronary intervention (PCI) in selected patients with ST-segment elevation myocardial infarction (STEMI). Whether both bolus and infusion are necessary to improve outcomes is unknown. We hypothesized that primary PCI with eptifibatide bolus only is non-inferior to the conventional treatment (bolus and infusion) with regard to infarct size, while reducing bleeding complications. We analyzed 720 consecutive STEMI patients receiving eptifibatide bolus only or conventional treatment in an observational case-control study utilizing propensity score matching of clinical and intervention-specific confounders. Infarct size was estimated based on myocardial bound creatine kinase, creatine kinase (CK), and CK area under the curve values, with a prespecified non-inferiority margin of 20%. Major bleeding was defined as type 2, 3, or 5 on the Bleeding Academic Research Consortium classification. Eptifibatide bolus only was administered to 147 patients (20%), which were matched 1:1 to patients receiving conventional treatment. Based on peak myocardial bound creatine kinase, CK and CK area under the curve values, infarct size was -8.4% (95% CI [-31.2%, 14.4%]), -11.6% (95% CI [-33.5%, 10.3%]), and -13.9% (95% CI [-34.1%, 6.2%]) after eptifibatide bolus, respectively, reaching prespecified noninferiority compared with conventional treatment. Bolus treatment significantly reduced major bleeding complications (OR 0.48, 95% CI [0.30, 0.79]). In conclusion, eptifibatide given as abbreviated bolus only to selected STEMI patients who underwent primary PCI was noninferior regarding infarct size and resulted in less bleeding complications compared with conventional bolus and infusion treatment.

Differences in presentation and clinical outcomes between left or right bundle branch block and ST segment elevation in patients with acute myocardial infarction.

BACKGROUND: In patients with acute myocardial infarction, the presence of a left bundle branch block or right bundle branch block may be associated with worse prognosis compared to isolated ST segment elevation. However, specificities in clinical presentation and outcomes of acute myocardial infarction patients with left bundle branch block or right bundle branch block are poorly characterized. METHODS: We analysed acute myocardial infarction patients with left bundle branch block (n=880), right bundle branch block (n=732) or ST segment elevation without bundle branch block (n=15,852) included in the Acute Myocardial Infarction in Switzerland-Plus registry between 2008-2019. RESULTS: Acute myocardial infarction patients with bundle branch block were older and had more pre-existing cardiovascular conditions compared to ST segment elevation. Pulmonary oedema and cardiogenic shock were most frequent in patients with left bundle branch block (18.8% vs 12.0% for right bundle branch block and 7.9% for ST segment elevation, p<0.001). Acute myocardial infarction patients with bundle branch block had more three-vessel (40.6% vs 25.3%, p<0.001 vs ST segment elevation) and left main disease (5.6% vs 2.0%, p<0.001 vs ST segment elevation). Major adverse cardiac and cerebrovascular events, a composite of reinfarction, stroke/transient ischaemic attack, and death during hospitalization, were highest in acute myocardial infarction patients with left bundle branch block (13.9% vs 9.9% for right bundle branch block and 6.7% for ST segment elevation, p<0.05), which was driven by hospital mortality. After multivariate adjustment, however, mortality was similar in patients with left bundle branch block and lower in patients with right bundle branch block, respectively, when compared to ST segment elevation. Mortality was only increased when a right bundle branch block with concomitant STE was present (odds ratio 1.77, 95% confidence interval 1.19-2.64, p<0.01 vs ST segment elevation). CONCLUSIONS: Compared to ST segment elevation, an isolated bundle branch block reflects high-risk clinical characteristics but does not independently determine increased hospital mortality in acute myocardial infarction.

Nox1 downregulators: A new class of therapeutics.

Chronic non-communicable diseases share the pathomechanism of increased reactive oxygen species (ROS) production by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, known as Nox. The recent discovery that expression of Nox1, a Nox isoform that has been implicated in the pathogenesis of cardiovascular and kidney disease and cancer is regulated by the expression and activity of G protein-coupled estrogen receptor (GPER) led to the identification of orally active small-molecule GPER blockers as selective Nox1 downregulators (NDRs). Preclinical studies using NDRs have demonstrated beneficial effects in vascular disease, hypertension, and glomerular renal injury. These findings suggest the therapeutic potential of NDRs, which reduce Nox1 protein levels, not only for cardiovascular disease conditions including arterial hypertension, pulmonary hypertension, heart failure with preserved ejection fraction (HFpEF), and chronic renal disease, but also for other non-communicable diseases, such as cerebrovascular disease and vascular dementia, Alzheimer's disease, autoimmune diseases and cancer, in which elevated Nox1-derived ROS production plays a causal role.

Gender differences in patient and system delay for primary percutaneous coronary intervention: current trends in a Swiss ST-segment elevation myocardial infarction population.

BACKGROUND: Women with ST-segment elevation myocardial infarction (STEMI) experience greater delays for percutaneous coronary intervention-facilitated reperfusion than men. Whether women and men benefit equally from current strategies to reduce ischaemic time and whether there are gender differences in factors determining delays is unclear. METHODS: Patient delay (symptom onset to first medical contact) and system delay (first medical contact to percutaneous coronary intervention-facilitated reperfusion) were compared between women ( n=967) and men ( n=3393) in a Swiss STEMI treatment network. Trends from 2000 to 2016 were analysed, with additional comparisons between three time periods (2000-2005, 2006-2011 and 2012-2016). Factors predicting delays and hospital mortality were determined by multivariate regression modelling. RESULTS: Female gender was independently associated with greater patient delay ( P=0.02 vs. men), accounting for a 12% greater total ischaemic time among women in 2012-2016 (median 215 vs. 192 minutes, P<0.001 vs. men). From 2000-2005 to 2012-2016, median system delay was reduced by 18 and 25 minutes in women and men, respectively ( P<0.0001 for trend, P=n.s. for gender difference). Total occlusion of the culprit artery, stent thrombosis, a Killip class of 3 or greater, and presentation during off-hours predicted delays in men, but not in women. A Killip class of 3 or greater and age, but not gender or delays, were independently associated with hospital mortality. CONCLUSIONS: STEMI-related ischaemic time in women remains greater than in men due to persistently greater patient delays. In contrast to men, clinical signs of ongoing chest discomfort do not predict delays in women, suggesting that female STEMI patients are less likely to attribute symptoms to a condition requiring urgent treatment.

Post-myocardial Infarction (MI) Care: Medication Adherence for Secondary Prevention After MI in a Large Real-world Population.

PURPOSE: Secondary medication prevention after acute myocardial infarction (MI) is strongly recommended in international guidelines, but actual use, adherence, and outcomes in current clinical practice are largely unknown. Therefore, the aims of this study were to determine the current adherence to medications for secondary prevention after MI and to estimate the association between medication adherence and mortality and major adverse cardiovascular events (MACE) in a large real-world population. METHODS: Using a large health care claims database, patients were selected who had been hospitalized with MI between 2012 and 2015 (N = 4349). Adherence to drug therapy after discharge was measured as the medication possession rate (MPR) per year (0%-100%, indicating the number of days with medication supplied relative to the total number of days) for the individual drug classes. The relationship between MPR and the risk of MACE and death was assessed by using Cox proportional hazards regression models. FINDINGS: A high proportion of patients with low MPR (0%-79%) was observed for all drug classes (47.6% for dual antiplatelet therapy (DAPT), 23.5% for lipid-lowering drugs (LLDs), 47.3% for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 88.1% for beta-blockers (BB). Women and elderly patients were less likely to receive LLDs. Patients with high adherence to DAPT, LLDs, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (MPR ≥80%) had a significantly reduced risk for all-cause mortality and MACE (LLD-group). IMPLICATIONS: In a real-life setting, adherence to drug therapy for secondary cardiovascular prevention after MI was only moderate. Increased use of evidence-based treatment such as DAPT and LLDs in current clinical practice may improve long-term outcomes of patients with MI. Moreover, providing clear information, improved care transition, and a close collaboration between clinicians and physicians involved in an early outpatient follow-up is required.

Screening For Pulmonary Hypertension With Multidetector Computed Tomography Among Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation.

Aim: To assess the accuracy of multi-detector computed tomography (MDCT) derived pulmonary vessel measurements in predicting pulmonary hypertension (PH) among patients with severe symptomatic aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). Background: PH is common among patients with severe AS undergoing TAVI and is associated with adverse outcomes. MDCT is the imaging modality of choice to assess anatomical dimensions among patients selected for TAVI. Methods: One hundred and thirty-nine patients with severe AS undergoing TAVI with both CT scans and right heart catheterizations (RHC) were included. CT diameters of the main pulmonary artery (MPA), right (RPA) and left (LPA), and ascending aorta (AA) were measured. The relationship between CT measurements and PA pressures assessing using RHC was tested with linear regression. Results: The CT derived ratio of the diameter of the MPA to the diameter of the AA (PA/AAratio) correlated best with mean PA pressure (R2 = 0.48) and PA systolic pressure (R2 = 0.50). Receiver operating characteristic curve analysis showed that the PA/AAratio is a moderate predictor of PH (AUC 0.74, 95% CI 0.65-0.83, p < 0.0001) and that the optimal cut off point is 0.80 (sensitivity 56%, specificity 88%, positive predictive value 95.5%, negative predictive value 30.6% for PH). Conclusions: Elderly patients with severe AS and PA/AAratio values ≥ 0.80 on MDCT are more likely to have PH but PH cannot be reliably excluded among such patients with lower PA/AAratio values.

Role of GPER in estrogen-dependent nitric oxide formation and vasodilation.

Estrogens are potent regulators of vasomotor tone, yet underlying receptor- and ligand-specific signaling pathways remain poorly characterized. The primary physiological estrogen 17ß-estradiol (E2), a non-selective agonist of classical nuclear estrogen receptors (ERα and ERß) as well as the G protein-coupled estrogen receptor (GPER), stimulates formation of the vasodilator nitric oxide (NO) in endothelial cells. Here, we studied the contribution of GPER signaling in E2-dependent activation of endothelial NO formation and subsequent vasodilation. Employing E2 and the GPER-selective agonist G-1, we investigated eNOS phosphorylation and NO formation in human endothelial cells, and endothelium-dependent vasodilation in the aortae of wild-type and Gper-deficient mice. Both E2 and G-1 induced phosphorylation of eNOS at the activation site Ser1177 to similar extents. Endothelial NO production to E2 was comparable to that of G-1, and was substantially reduced after pharmacological inhibition of GPER. Similarly, the clinically used ER-targeting drugs 4OH-tamoxifen, raloxifene, and ICI182,780 (faslodex, fulvestrant™) induced NO formation in part via GPER. We identified c-Src, EGFR, PI3K and ERK signaling pathways to be involved in GPER-dependent NO formation. In line with activation of NO formation in cells, E2 and G-1 induced equally potent vasodilation in the aorta of wild-type mice. Gper deletion completely abrogated the vasodilator response to G-1, while reducing the response to E2 by ∼50%. These findings indicate that a substantial portion of E2-induced endothelium-dependent vasodilation and NO formation is mediated by GPER. Thus, selective targeting of vascular GPER may be a suitable approach to activate the endothelial NO pathway, possibly leading to reduced vasomotor tone and inhibition of atherosclerotic vascular disease.

GPER blockers as Nox downregulators: A new drug class to target chronic non-communicable diseases.

Oxidative stress is a hallmark of chronic non-communicable diseases such as arterial hypertension, coronary artery disease, diabetes, and chronic renal disease. Cardiovascular diseases are characterized by increased production of reactive oxygen species (ROS) by NAPDH oxidase 1 (Nox1) and additional Nox isoforms among other sources. Activation of the G protein-coupled estrogen receptor (GPER) can mediate multiple salutary effects on the cardiovascular system. However, GPER also has constitutive activity, e.g. in the absence of specific agonists, that was recently shown to promote hypertension and aging-induced tissue damage by promoting Nox1-derived production of ROS. Furthermore, the small molecule GPER blocker (GRB) G36 reduces blood pressure and vascular ROS production by selectively down-regulating Nox1 expression. These unexpected findings revealed GRBs as first in class Nox downregulators capable to selectively reduce the increased expression and activity of Nox1 in disease conditions. Here, we will discuss the paradigm shift from selective GPER activation to ligand-independent, constitutive GPER signaling as a key regulator of Nox-derived oxidative stress, and the surprising identification of GRBs as the first Nox downregulators for the treatment of chronic non-communicable diseases.

GPER Mediates Functional Endothelial Aging in Renal Arteries.

Aging is associated with impaired renal artery function, which is partly characterized by arterial stiffening and a reduced vasodilatory capacity due to excessive generation of reactive oxygen species by NADPH oxidases (Nox). The abundance and activity of Nox depends on basal activity of the heptahelical transmembrane receptor GPER; however, whether GPER contributes to age-dependent functional changes in renal arteries is unknown. This study investigated the effect of aging and Nox activity on renal artery tone in wild-type and GPER-deficient (Gper-/-) mice (4 and 24 months old). In wild-type mice, aging markedly impaired endothelium-dependent, nitric oxide (NO)-mediated relaxations to acetylcholine, which were largely preserved in renal arteries of aged Gper-/- mice. The Nox inhibitor gp91ds-tat abolished this difference by greatly enhancing relaxations in wild-type mice, while having no effect in Gper-/- mice. Contractions to angiotensin II and phenylephrine in wild-type mice were partly sensitive to gp91ds-tat but unaffected by aging. Again, deletion of GPER abolished effects of Nox inhibition on contractile responses. In conclusion, basal activity of GPER is required for the age-dependent impairment of endothelium-dependent, NO-mediated relaxation in the renal artery. Restoration of relaxation by a Nox inhibitor in aged wild-type but not Gper-/- mice strongly supports a role for Nox-derived reactive oxygen species as the underlying cause. Pharmacological blockers of GPER signaling may thus be suitable to inhibit functional endothelial aging of renal arteries by reducing Nox-derived oxidative stress and, possibly, the associated age-dependent deterioration of kidney function.

Efficacy and safety of transcatheter closure in adults with large or small atrial septal defects.

BACKGROUND: In most patients with secundum atrial septal defects (ASD), transcatheter closure is the preferred treatment strategy, but whether device size affects clinical outcomes is unknown. We sought to study the efficacy and safety of large closure devices compared to the use of smaller devices. METHODS: Using a single-center, prospective registry of adult patients undergoing transcatheter ASD closure, patients receiving a large closure device (waist diameter ≥25 mm, n = 41) were compared to patients receiving smaller devices (waist diameter ≤24 mm, n = 66). We analyzed pre-interventional clinical, hemodynamic and echocardiographic data, interventional success and complication rates, and 6-month clinical and echocardiographic outcomes. The primary efficacy outcome was successful ASD closure achieved by a single procedure and confirmed by lack of a significant residual shunt at 6 months. The primary safety outcome was a composite of device embolization, major bleeding, and new-onset atrial arrhythmia occurring within 6 months. RESULTS: Transcatheter ASD closure using large devices was successful in 90 % compared to 97 % of patients receiving smaller devices as defined by the primary efficacy outcome (p = 0.20). The primary safety outcome occurred in 4 patients of the large and 6 patients of the small device group, resulting in an event-free rate of 90 and 91 %, respectively (p = 0.89). Similar significant symptomatic improvement was observed in both treatment groups after 6 months, indicated by a 50 % increase in the fraction of patients in NYHA class I (p < 0.0001 vs. baseline). CONCLUSIONS: Transcatheter closure in this cohort of patients with large or small ASD was effective with similar complication rates during short-term follow-up irrespective of the size of the implanted device.

Obligatory role for GPER in cardiovascular aging and disease.

Pharmacological activation of the heptahelical G protein-coupled estrogen receptor (GPER) by selective ligands counteracts multiple aspects of cardiovascular disease. We thus expected that genetic deletion or pharmacological inhibition of GPER would further aggravate such disease states, particularly with age. To the contrary, we found that genetic ablation of Gper in mice prevented cardiovascular pathologies associated with aging by reducing superoxide (⋅O2-) formation by NADPH oxidase (Nox) specifically through reducing the expression of the Nox isoform Nox1 Blocking GPER activity pharmacologically with G36, a synthetic, small-molecule, GPER-selective blocker (GRB), decreased Nox1 abundance and ⋅O2- production to basal amounts in cells exposed to angiotensin II and in mice chronically infused with angiotensin II, reducing arterial hypertension. Thus, this study revealed a role for GPER activity in regulating Nox1 abundance and associated ⋅O2--mediated structural and functional damage that contributes to disease pathology. Our results indicated that GRBs represent a new class of drugs that can reduce Nox abundance and activity and could be used for the treatment of chronic disease processes involving excessive ⋅O2- formation, including arterial hypertension and heart failure.

Accelerated Vascular Aging as a Paradigm for Hypertensive Vascular Disease: Prevention and Therapy.

Aging is considered the most important nonmodifiable risk factor for cardiovascular disease and death after age 28 years. Because of demographic changes the world population is expected to increase to 9 billion by the year 2050 and up to 12 billion by 2100, with several-fold increases among those 65 years of age and older. Healthy aging and prevention of aging-related diseases and associated health costs have become part of political agendas of governments around the world. Atherosclerotic vascular burden increases with age; accordingly, patients with progeria (premature aging) syndromes die from myocardial infarctions or stroke as teenagers or young adults. The incidence and prevalence of arterial hypertension also increases with age. Arterial hypertension-like diabetes and chronic renal failure-shares numerous pathologies and underlying mechanisms with the vascular aging process. In this article, we review how arterial hypertension resembles premature vascular aging, including the mechanisms by which arterial hypertension (as well as other risk factors such as diabetes mellitus, dyslipidemia, or chronic renal failure) accelerates the vascular aging process. We will also address the importance of cardiovascular risk factor control-including antihypertensive therapy-as a powerful intervention to interfere with premature vascular aging to reduce the age-associated prevalence of diseases such as myocardial infarction, heart failure, hypertensive nephropathy, and vascular dementia due to cerebrovascular disease. Finally, we will discuss the implementation of endothelial therapy, which aims at active patient participation to improve primary and secondary prevention of cardiovascular disease.