Therapeutic Advances in Cardiovascular Disease最新文献

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are a relatively new class of antihyperglycemic drug with salutary effects on glucose control, body weight, and blood pressure. Emerging evidence now indicates that these drugs may have a beneficial effect on outcomes in heart failure with reduced ejection fraction (HFrEF). Post-approval cardiovascular outcomes data for three of these agents (canagliflozin, empagliflozin, and dapagliflozin) showed an unexpected improvement in cardiovascular endpoints, including heart failure hospitalization and mortality, among patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease or risk factors. These studies were followed by a placebo controlled trial of dapagliflozin in patients with HFrEF both with and without T2DM, showing a reduction in all-cause mortality comparable to current guideline-directed HFrEF medical therapies such as angiotensin-converting enzyme inhibitors and beta-blockers. In this review, we discuss the current landscape of evidence, safety and adverse effects, and proposed mechanisms of action for use of these agents for patients with HFrEF. The United States (US) and European guidelines are reviewed, as are the current US federally approved indications for each SGLT2 inhibitor. Use of these agents in clinical practice may be limited by an uncertain insurance environment, especially in patients without T2DM. Finally, we discuss practical considerations for the cardiovascular clinician, including within-class differences of the SGLT2 inhibitors currently available on the US market (217/300).

The novel severe acute respiratory syndrome viral disease outbreak due to SARS-CoV-2 is a rapidly evolving disease and represents one of the greatest medical challenges in recent times. It is believed that SARS-CoV-2 has migrated from bats to an intermediate host and then to humans. This article aims at the mechanism and management of prothrombotic state in COVID-19 positive patients. We tried to present how the SARS-CoV-2 virus can induce thromboembolic events and the incidence of these thromboembolic events. We also tried to depict anticoagulation management in these patients as well as postdischarge plan and follow-up. Invasion of type 2 pneumocytes by the SARS-CoV-2 virus is critical in the course of illness because it results in activation of immune cells leading to elevation of cytokines. The subsequent activation of T cells and macrophages infiltrates the infected myocardial cells causing direct myocardiocyte toxicity and development of arrhythmia. Hypoxia or hypotension during the clinical course causes a mismatch between myocyte oxygen supply and workload demand resulting in cardiac distress. SARS-CoV-2 affects endothelial cells and pericytes that lead to severe micro and macrovascular dysfunction, and together with oxygen supply-demand mismatch, immune hyperresponsivity can potentially cause destabilization and plaque rupture causing acute coronary syndromes. Other mechanisms of injury include myocarditis, pericarditis, stress cardiomyopathy, vasculitis, and DIC (Disseminated intravascular coagulation)/microthrombi. SARS-CoV-2 enters the cells by the Spike protein S whose surface unit, S1, binds to the ACE2 receptor on the host cell. The type II transmembrane serine proteases TMPRSS2 and histone acetyltransferases (HAT) are host cell proteases that are recruited by the virus to cleave ACE2 surface protein S which facilitates the viral entry. Therefore, TMPRSS2 and HAT could be targeted for potential drugs against SARS-CoV-2. SARS-CoV-2 uses an RNA-dependent RNA polymerase for proliferation, which is targeted by remdesivir that is currently approved for emergency use by Food and Drug Administration (FDA). We need to adopt a multifaceted approach when combating SARS-CoV-2 because it presents several challenges including medical, psychological, socioeconomic, and ethical. COVID-19 is the biggest calamity during the 21st century, we need to have a keen understanding of its pathophysiology and clinical implications for the development of preventive measures and therapeutic modalities.

Background: We aimed to investigate the safety of endovascular procedures undertaken in a single outpatient center located in a rural, underserved area. Endovascular procedures for Peripheral Arterial Disease (PAD) have become increasingly common in outpatient settings; their safety is yet to be determined in a rural, underserved area with no stand-by vascular surgeon on site.

Methods: We undertook a retrospective case review of endovascular procedures for the investigation and management of lower extremity PAD between December 2012 and August 2015. Patients were classified by Rutherford score, degree of stenosis and length of lesions. Complications were major (requiring hospitalization) or minor, including perforation, distal embolization, hematoma, and allergic reactions, which could be treated immediately in the catheterization laboratory with no sequelae. Patients were monitored in the facility and followed up using clinical, biochemical and radiological parameters at 24 h and 1 month.

Results: A total of 692 patients underwent endovascular procedures for the investigation and/or treatment of PAD, of which 608 were interventional. Of these patients, 10.20% experienced procedural complications, of which 0.66% were classified as major, including wire retention and retroperitoneal hemorrhage. In total, 99.34% were discharged safely on the same day as the procedure. No adverse events were reported at follow up.

Conclusion: Endovascular procedures for PAD can be performed safely in a rural outpatient setting with low complication rates. Most complications are minor and do not require hospitalization. Outpatient procedures for PAD are safe and may widen access to specialist procedures in areas of socio-economic deprivation.

Background: The objective of this review is to provide a practical update on endpoint selection for noninferiority (NI) studies in percutaneous coronary intervention studies.

Methods: A PubMed search was conducted for predefined terms to explore the use of NI designs and intrapatient comparisons to determine their current importance. Sample size calculations for the most frequently used endpoints with NI hypotheses were done to increase statistical awareness.

Results: Reported NI trials, with the most frequently chosen clinical endpoint of major adverse cardiac events (MACE), had NI margins ranging from 1.66% to 5.00%, resulting in patient populations of 400-1500 per treatment group. Clinical study endpoints comprising of MACE complemented with rates of bleeding complications and stent thrombosis (ST) are suggested to conduct a statistically and clinically meaningful NI trial. Study designs with surrogate endpoints amenable to intrapatient randomizations, are a very attractive option to reduce the number of necessary patients by about half. Comparative clinical endpoint studies with MACE and ST/bleeding rates to study a shortened dual antiplatelet therapy (DAPT) in coronary stent trials are feasible, whereas ST as the sole primary endpoint is not useful.

Conclusions: Expanded composite clinical endpoints (MACE complemented by ST and bleeding rates and intrapatient randomization for selected surrogate endpoints) may be suitable tools to meet future needs in device approval, recertification and reimbursement.

Introduction: Thyroid hormone (TH) has an essential role on the functional capability of cardiac muscle with its gene modulation and induction of vasodilatory effects. There is considerable evidence to suggest the role of TH in patients with acute coronary syndrome, but less is known about its prognostic role in heart failure (HF) patients. We aim to evaluate the association between subclinical hypothyroid state (SCHS) and event rates including 30-day all-cause and HF readmission in patients with an index hospitalization for acute HF syndrome (AHFS).

Methodology: A retrospective chart review analysis of 2335 patients admitted with the diagnosis of AHFS between 1 January 2007 and 31 December 2017 was conducted. SCHS was defined as thyroid-stimulating hormone (TSH) level >4.50 mIU/L with a normal thyroxine (T₄) level. Patients with pre-existing thyroid disease or receiving thyroid replacement therapy were excluded. HF with preserved ejection fraction (HFpEF) was defined as left ventricular ejection fraction (LVEF) >40% and HF with reduced ejection fraction (HFrEF) was defined as having LVEF ⩽40%. Percentage of 30-day, 3-month and 6-month all-cause readmission and mortality rates were calculated in both cohorts of AHFS (HFpEF and HFrEF) with and without SCHS.

Results: The mean age of the 2335 AHFS population was 65 (±14.8) years. Of the 2335 patients admitted with AHFS, 1228 (52.6%) patients were found to have HFrEF and 1107 (47.4%) with HFpEF. There were 170 (7.3%) patients with AHFS found to have SCHS. There were more males than females (54% versus 46%). The percentage of hospital readmission within 30 days was higher for patients with SCHS compared with those without SCHS in the HFrEF group (42% versus 30%, p = 0.001). Hospital readmission within 30 days for patients with SCHS compared with those without SCHS in the HFpEF group did not differ (36.5% versus 31%, p = 0.47). Additionally, all-cause mortality was higher among patients with SCHS compared with patients without SCHS in the HFrEF group (18.7% versus 7.0%, p < 0.001). All-cause mortality was found similar in both arms of the HFpEF group (9.5% versus 7.7%, p = 0.73).

Conclusion: During an index hospital admission for AHFS, SCHS was an independent predictor of readmission in 30 days in patients with HFrEF but not in patients with HFpEF. Additionally, it was related to adverse outcome such as all-cause mortality in HFrEF patients but not in HFpEF patients. Further studies regarding the concept of tissue thyroid and the potential for a therapeutic target are warranted.

COVID-19 is said to be a pandemic that does not distinguish between skin color or ethnic origin. However, data in many parts of the world, especially in the United States, begin to show that there is a sector of society suffering a more significant impact from this pandemic. The Black population is more vulnerable than the White population to infection and death by COVID-19, with hypertension and diabetes mellitus as probable predisposing factors. Over time, multiple disparities have been observed between the health of Black and White populations, associated mainly with socioeconomic inequalities. However, some mechanisms and pathophysiological susceptibilities begin to be elucidated that are related directly to the higher prevalence of multiple diseases in the Black population, including infection and death by COVID-19. Plasma vitamin D levels and evolutionary adaptations of the renin-angiotensin-aldosterone system (RAAS) in Black people differ considerably from those of other races. The role of these factors in the development and progression of hypertension and multiple lung diseases, among them SARS-CoV-2 infection, is well established. In this sense, the present review attempts to elucidate the link between vitamin D and RAAS ethnic disparities and susceptibility to infection and death by COVID-19 in Black people, and suggests possible mechanisms for this susceptibility.

Background: Little is known about the extent to which routine care management of peripheral arterial disease (PAD) and intermittent claudication (IC) align with best practice recommendations on exercise therapy. We conducted a scoping review to examine the published literature on the availability and workings of exercise therapy in the routine management of patients with PAD and IC, and the attitude and practice of health professionals and patients.

Methods: A systematic search was conducted in February 2018. The Cumulative Index of Nursing and Allied Health Literature, Ovid MEDLINE, Allied and Complementary Medicine Database, ScienceDirect, Web of Science and the Directory of Open Access Repositories were searched. Hand searching of reference lists of identified studies was also performed. Inclusion criteria were based on study aim, and included studies that reported on the perceptions, practices, and workings of routine exercise programs for patients with IC, their availability, access, and perceived barriers.

Results: Eight studies met the eligibility criteria and were included in the review. Studies conducted within Europe were included. Findings indicated that vascular surgeons in parts of Europe generally recognize supervised exercise therapy as a best practice treatment for IC, but do not often refer their patients for supervised exercise therapy due to the unavailability of, or lack of access to supervised exercise therapy programs. Available supervised exercise therapy programs do not implement best practice recommendations, and in the majority, patients only undergo one session per week. Some challenges were cited as the cause of the suboptimal program implementation. These included issues related to patients' engagement and adherence as well as resource constraints.

Conclusion: There is a dearth of published research on exercise therapy in the routine management of PAD and IC. Available data from a few countries within Europe indicated that supervised exercise is underutilized despite health professionals recognizing the benefits. Research is needed to understand how to improve the availability, access, uptake, and adherence to the best exercise recommendations in the routine management of people with PAD and IC.

Background: Endovascular therapy for acute lower limb ischemia (ALLI) has developed and demonstrated safety and efficacy. The purpose of this study was to assess clinical outcomes in patients treated for ALLI with conventional endovascular or surgical revascularization.

Method: This study was a retrospective single-center review. Consecutive patients with ALLI treated with conventional endovascular revascularization (ER) without thrombolytic agent or surgical revascularization (SR) between 2008 and 2014 were investigated. The 1 year and 3 year amputation rate and mortality rate were assessed by time-to-event methods, including Kaplan-Meier estimation.

Result: A total of 64 limbs in 62 patients with ALLI due to thromboembolism or thrombosis of a native artery, bypass graft, or previous stented vessel were included. The majority of limbs (90.9%) presented with Rutherford clinical categories 1 to 2 ischemia. Technical success rate was 95.5% in ER and 92.9% in SR group (p = 0.547). Overall amputation rates were 9.1% in ER versus 9.5% in SR after 1 year (p = 0.971) and 9.1% in ER versus 11.9% in SR after 3 year (p = 0.742). Overall mortality rates were 15% in ER versus 7.1% in SR after 1 year (p = 0.491) and 15% in ER versus 11.2% in SR after 3 year (p = 0.878).

Conclusion: Endovascular or surgical revascularization of ALLI resulted in comparable outcomes in limb salvage and mortality rate at 1 year and 3 year. Conventional endovascular therapy without thrombolytic agent such as stenting, balloon angioplasty, or catheter-directed thrombosuction may be considered as a treatment option for ALLI.