Reduction In All-cause Mortality Research Articles

Systematic review and meta-analysis of early aortic valve replacement versus conservative therapy in patients with asymptomatic aortic valve stenosis with preserved left ventricle systolic function

BackgroundA quarter of patients with severe aortic stenosis (AS) were asymptomatic, and only a third of them survived at the end of 4 years. Only a select subset of these...

The impact of extracorporeal membrane oxygenation on mortality in patients with cardiogenic shock post-acute myocardial infarction: a systematic review and meta-analysis.

Cardiogenic shock remains the leading cause of death in patients hospitalized with acute myocardial infarction. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in the treatment of infarct-related cardiogenic shock. However, there is limited evidence regarding its beneficial impact on mortality. The aim of this study was to systematically review studies reporting the impact of VA-ECMO on mortality in patients with acute myocardial infarction complicated by cardiogenic shock. A comprehensive search of medical databases (Cochrane Register and PubMed) was conducted. Studies that reported mortality outcomes in patients treated with VA-ECMO for infarct-related cardiogenic shock were included. The database search yielded 1194 results, of which 11 studies were included in the systematic review. Four of these studies, with a total of 586 patients, were randomized controlled trials and were included in the meta-analysis. This demonstrated that there was no significant difference in 30-day all-cause mortality with the use of VA-ECMO compared with standard medical therapy [odds ratio (OR) 0.91; 95% confidence interval (CI) 0.65-1.27]. Meta-analysis of two studies showed that VA-ECMO was associated with a significant reduction in 12-month all-cause mortality (OR 0.31; 95% CI 0.11-0.86). Qualitative synthesis of the observational studies showed that age, serum creatinine, serum lactate, and successful revascularization are independent predictors of mortality. Veno-arterial extracorporeal membrane oxygenation does not improve 30-day all-cause mortality in patients with cardiogenic shock following acute myocardial infarction; however, there may be significant reduction in all-cause mortality at 12 months. Further studies are needed to delineate the potential benefit of VA-ECMO in long-term outcomes. The protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42023461740).

HerzMobil Tirol – A telemedical, integrated disease management program for patients with heart failure

Heart failure (HF) is a global health problem with an increasing an increasing incidence and prevalence and thus a major impact on healthcare systems. The 1-year mortality is 23.6% in patients with acute HF. Hospitalization for acute HF is associated with higher mortality and recurrent hospitalization. The majority of readmissions occurs early after hospital discharge: about 25% of patients are readmitted within the first month with a 50% proportion of HF-related causes of readmissions.
 Therefore, in 2012 the Austrian province of Tyrol launched the HerzMobil Tirol (HMT) program, which is a multidisciplinary post-discharge disease management program for HF patients. It is supported by a telemedical monitoring system and embedded in a network of specialized nurses, resident physicians, and secondary/tertiary referral centers. After initial project phases, HMT reached its adolescence in 2017 and was adopted as regular service. This ensures reimbursement of the program by the social security system. 
 HMT is based on: (1) patient education to improve patient empowerment, (2) nurse-led care for early detection of imminent decompensation, (3) patient-held mobile phone for daily data acquisition and transmission of blood pressure, heart rate, body weight, well-being and drug intake, including nurse and physician-controlled telemonitoring, (4) continuous optimization of guideline-based HF therapy for long-term stabilization, and (5) network communication to assure comprehensive HF management across venues;
 Patients enter HMT at the end of hospitalization for acute HF. Patient education is delivered by specialized HF nurses. On discharge, each patient is assigned to a resident network physician near his/her home. Network physicians supervise the management of the patient and optimize individualized guideline-directed medical therapy. Discharge information including a detailed treatment plan from the hospital is communicated to the HMT network. Within HMT, patients are supervised for 3 months. Telemedically transmitted patient data are reviewed daily by HF nurses and weekly by network physicians. Out-of-limit data are automatically signaled so that interventions, for example, adjustment of diuretics, can follow immediately. Face-to-face visits of the patient with the network physician are scheduled 1, 4, and 12 weeks after discharge. HF nurses monitor patients’ compliance with medication, maintain telephone contact with patients if necessary and adjust HF medication according to the network physicians’ instructions. Additionally, a home visit by the HF nurse is scheduled immediately after discharge to complete disease- and equipment-related education and to ensure that prescribed medication is available. At the end of the managed care program, structured transfer of patients to regular care is organized. Regular HF network meetings of physicians and nurses are scheduled every 3 months.
 A recently publication demonstrated the effectiveness of the program as indicated by a significant reduction of HF readmission and all-cause mortality within 6 months for patients in the HMT program compared to usual-care patients. 
 HerzMobil was adopted in other provinces of Austria following the Tyrolean model. It is continuously further developed. In a next step, the coronary heart disease will be included in the HMT model. An extension of the program with physical activity aspects is planned.

Effect of renin angiotensin system inhibitors on long-term major cardiovascular outcomes in patients with high atherosclerotic cardiovascular risk

The advantage of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) in patients with preserved LV systolic function is uncertain. We aimed to investigate the effects of ACEI/ARB in high atherosclerotic risk patients without overt heart failure (HF) on long-term major cardiovascular outcomes (MACEs). The Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand) registry is a prospective, multicenter, observational, longitudinal study of Thai patients with high atherosclerotic risk. The patients with ejection fraction < 50% were excluded. Among 8513 recruited patients, there were 4246 patients included into final analysis after propensity score matching. At 5-years follow-up, Cox regression analysis showed that ACEI/ARB was significantly associated with reduced risk of all-cause mortality or non-fatal myocardial infarction, non-fatal stroke and HF hospitalization (HR 0.82, 95% CI 0.70–0.96, P = 0.011). The benefit was driven by the reduced all-cause mortality and HF. Subgroup analysis demonstrated that ACEI/ARB decreased risk of long-term MACEs in patients with diabetes (HR 0.77, 95% CI 0.63–0.94, P = 0.011) and patients not taking statin (HR 0.57, 95% CI 0.40–0.82, P = 0.002). We demonstrated that the use of ACEI/ARB was associated with reduced risk of long-term MACEs in a large cohort of high atherosclerotic risk patients. Reduction of all-cause mortality and HF were likely the main contributors to the benefit of ACEI/ARB.

Reducing the hospitalization epidemic of chronic heart failure by disease management programs.

Chronic heart failure is the most common cause of hospitalization in Europe and rates are steadily increasing due to aging of the population. Hospitalization identifies a fundamental change in the natural history of heart failure (HF) increasing the risk of re-hospitalization and mortality. Heart failure management programs improve the quality of care for HF patients and reduce hospitalization burden. The goals of the heart failure management programs include optimization of drug therapy, patient education, early recognition of signs of decompensation, and management of comorbidities. Randomized clinical trials evidenced that system of care for heart failure patients improved adherence to treatment and reduced unplanned re-admissions to hospital. Multidisciplinary programs and home-visiting have shown improved efficacy with reductions in HF and all-cause hospitalizations and mortality. Community HF clinics should take care of the management of stable patients in strict contact with primary care, while hospital out-patients clinics should care of patients with severe disease or persistent clinical instability, candidates to advanced treatment options. In any case a holistic, patient-centered approach is suggested, to optimize care considering the needs of the individual patient. Telemonitoring is a new opportunity for HF patients, because it allows the continuity of care at home. All heart failure patients should require follow-up in a specific management program, but most of date come from clinical trials that included high-risk patients. While clinical trials have a specified duration (from months to some years), lifelong follow-up is recommended with differentiated approaches according to the patient's need.

Effectiveness of Cardiac Rehabilitation Services in Low- and Middle-Income Countries: A Systematic Review.

Cardiac rehabilitation (CR) is a cost-effective intervention that can reduce cardiovascular disease (CVD) morbidity and mortality by 20%. Despite the clear benefits of CR, it remains unavailable and underutilized. This study aimed to assess the effectiveness of different CR models in reducing CVD-related morbidity and mortality in low-and middle-income countries. We conducted a systematic review of studies conducted in low- and middle-income countries that assessed at least one of the three phases of CR (inpatient rehabilitation, outpatient rehabilitation in a hospital, or community setting and maintenance). The primary outcomes of interest were mortality (all-cause and CVD-specific), CVD-related morbidity, functional capacity, risk factor reduction, and quality of life (QoL). The electronic search retrieved 1,102 studies, of which 22 were retrieved and included in the review. These studies were conducted between 2011 and 2022 and the majority (18) were conducted in Asia. All studies except one were randomized controlled trials (RCTs), and all except one were conducted at a single site. The target population in most studies (16) included patients with coronary artery disease (CAD). Seven studies have incorporated digital technology. Only one study has reported a significant reduction in all-cause mortality. Thirteen studies reported data on functional capacity, and 16 on quality of life (QoL), showing statistically significant improvements. Data on risk factors, anxiety, and depression have shown mixed results. CR is effective in low- and middle-income countries, and strategies to scale it up using locally available resources tailored to the patient population should be adopted.

Treatment Strategies for Chronic Coronary Heart Disease with Left Ventricular Systolic Dysfunction or Preserved Ejection Fraction-A Systematic Review and Meta-Analysis.

We conducted a systematic search to identify all randomized trials directly comparing invasive strategies with optimal medical therapy (OMT) in patients diagnosed with chronic CHD. Data from these trials were pooled using a random-effects meta-analysis. The primary outcome assessed was the all-cause mortality, while secondary endpoints included cardiovascular (CV) death, stroke, myocardial infarction (MI), and unplanned revascularization. This study was designed to assess the benefits of both invasive strategies and OMT in patients with preserved LV function and in those with LV systolic dysfunction. The statistical analysis of the data was conducted using the Review Manager (RevMan) software, version 5.4.1 (The Cochrane Collaboration, 2020). Twelve randomized studies enrolling 13,912 patients were included in the final analysis. Among the patients with chronic CHD and preserved LV systolic function, revascularization did not demonstrate a reduction in all-cause mortality (8.52% vs. 8.45%, p = 0.45), CV death (3.41% vs. 3.62%, p = 0.08), or the incidence of MI (9.88% vs. 10.49%, p = 0.47). However, the need for unplanned myocardial revascularization was significantly lower in the group following the initial invasive approach compared to patients undergoing OMT (14.75% vs. 25.72%, p < 0.001). In contrast, the invasive strategy emerged as the preferred treatment modality for patients with ischemic LV systolic dysfunction. This approach demonstrated lower rates of all-cause mortality (40.61% vs. 46.52%, p = 0.004), CV death (28.75% vs. 35.82%, p = 0.0004), and MI (8.19% vs. 10.8%, p = 0.03). In individuals diagnosed with chronic CHD and preserved LV EF, the initial invasive approach did not demonstrate a clinical advantage over OMT. Conversely, in patients with ischemic LV systolic dysfunction, myocardial revascularization was found to reduce the risks of CV events and enhance the overall outcomes. These findings hold significant clinical relevance for optimizing treatment strategies in patients with chronic CHD, contingent upon myocardial contractility status.

Are sarcopenia and its individual components linked to all-cause mortality in heart failure? A systematic review and meta-analysis

Abstract Objective The objective of this systematic review and meta-analysis was to assess sarcopenia and its components as prognostic factors in patients with heart failure (HF). Methods From inception to December 2022, a systematic literature search was carried out utilizing PubMed, Web of Science, Scopus, and Cochrane Library databases. A meta-analysis employing a random-effects model was performed to assess the pooled effects. Results The systematic review and meta-analysis included 32 and 18 longitudinal studies, respectively. The prediction of 1- to 2-year all-cause mortality in sarcopenia was not statistically significant (hazard ratio (HR): 1.35, 95% CI 0.76–2.38, I2 = 54%, P = 0.31). The lowest combined quartile and quantile of the population were used to define low handgrip strength that showed identical results (HR: 1.24, 95% CI 0.94–1.62, I2 = 0%, P = 0.13). Low L3-L4 psoas muscle mass (HR: 2.20, 95% CI 1.26–3.83, I2 = 87%, P &lt; 0.01) and slow gait speed (HR: 1.45, 95% CI 1.20–1.74, I2 = 0%, P &lt; 0.01) were significant contributors to all-cause mortality risk. Additionally, a 0.1 m/s increase in gait speed demonstrated a significant reduction of all-cause mortality (HR: 0.77, 95% CI 0.66–0.90, I2 = 60%, P &lt; 0.01). Our narrative synthesis also described appendicular lean mass (ALM) and short physical performance battery (SPPB) scores as significant prognostic factors. Conclusions Compared to patients with higher overall functional performance, those with HF and low ALM, low psoas muscle mass, low SPPB, and slow gait speed are at an increased risk of all-cause mortality. Early prevention and/or treatment of lower limb physical function deterioration may be an essential strategy to reduce the risk of premature death in HF. Graphical abstract

Prolonged vs intermittent intravenous infusion of β-lactam antibiotics for patients with sepsis: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis

BackgroundThe prolonged β-lactam antibiotics infusion has been an attractive strategy in severe infections, because it provides a more stable free drug concentration and a longer duration of free drug concentration above the minimum inhibitory concentration (MIC). We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of prolonged vs intermittent intravenous infusion of β-lactam antibiotics for patients with sepsis.MethodsThis study was prospectively registered on PROSPERO database (CRD42023447692). We searched EMBASE, PubMed, and Cochrane Library to identify eligible studies (up to July 6, 2023). Any study meeting the inclusion and exclusion criteria would be included. The primary outcome was all-cause mortality within 30 days. Two authors independently screened studies and extracted data. When the I2 values < 50%, we used fixed-effect mode. Otherwise, the random effects model was used. TSA was also performed to search for the possibility of false-positive (type I error) or false-negative (type II error) results.ResultsA total of 4355 studies were identified in our search, and nine studies with 1762 patients were finally included. The pooled results showed that, compared with intermittent intravenous infusion, prolonged intravenous infusion of beta-lactam antibiotics resulted in a significant reduction in all-cause mortality within 30 days in patients with sepsis (RR 0.82; 95%CI 0.70–0.96; P = 0.01; TSA-adjusted CI 0.62–1.07). However, the certainty of the evidence was rated as low, and the TSA results suggested that more studies were needed to further confirm our conclusion. In addition, it is associated with lower hospital mortality, ICU mortality, and higher clinical cure. No significant reduction in 90-day mortality or the emergence of resistance bacteria was detected between the two groups.ConclusionsProlonged intravenous infusion of beta-lactam antibiotics in patients with sepsis was associated with short-term survival benefits and higher clinical cure. However, the TSA results suggested that more studies are needed to reach a definitive conclusion. In terms of long-term survival benefits, we could not show an improvement.

Association of bariatric surgery with indicated and unintended outcomes: An umbrella review and meta-analysis for risk-benefit assessment.

Bariatric surgery can cause numerous functional changes to recipients, some of which are unintended. However, a systematic evaluation of wide-angled health benefits and risks following bariatric surgery has not been conducted. We systematically evaluated published systematic reviews of randomized controlled trials and observational studies reporting the association between bariatric surgery and health outcomes. We performed subgroup analyses by surgery type and sensitivity analysis, excluding gastric band. Thirty systematic reviews and 82 meta-analyzed health outcomes were included in this review. A total of 66 (80%) health outcomes were significantly associated with bariatric surgery, of which 10 were adverse outcomes, including suicide, fracture, gastroesophageal reflux after sleeve gastrectomy, and neonatal morbidities. The other 56 outcomes were health benefits including new-onset diabetes mellitus (DM) (odds ratio [OR] =0.39; 95% confidence interval [CI] =0.19-0.79), hypertension (OR =0.36; 95% CI =0.33-0.40), dyslipidemia (OR =0.33; 95% CI =0.14-0.81), cancers (OR =0.65; 95% CI =0.53-0.80), cardiovascular diseases (CVDs), and women's health. Surgery is associated with reductions in all-cause mortality and death due to cancer, DM, and CVD. Bariatric surgery has both beneficial and harmful effects on a broader than expected array of patients' health outcomes. An expansion of the indication for bariatric surgery could be discussed to include a broader population with metabolic vulnerabilities.

Abstract C121: Follow-up of moderate and severe coronary artery calcifications identified on lung cancer screening CT scans: An opportunity to improve cardiac health outcomes in Black men and women

Abstract Background: The USPSTF currently recommends lung cancer screening (LCS) by low-dose CT (LDCT) in those 50 to 80 years of age with 20+ pack-years of smoking who are currently smoking or quit smoking within the last 15 years. LCS LDCT often detects non-cancer related incidental findings, most commonly coronary artery calcifications (CAC). CAC is a measure of subclinical coronary atherosclerosis, is higher in those with tobacco use, and may require additional clinical assessment after LCS. In the National Lung Screening Trial, reductions in all-cause mortality were stronger among Black than White participants undergoing LDCT. It was hypothesized that this may have been due to follow-up and treatment of incidental findings such as CAC during the trial. Methods: In this on-going observational study, we are evaluating clinical follow-up of moderate or severe CAC within 12 months of LCS among individuals undergoing baseline LCS at two Michigan health systems, one urban and one rural. We report here our initial findings for individuals with a baseline LCS LDCT at Henry Ford Health in 2018. Pearson Chi Square and McNemar’s tests were used to determine differences between race and sex groups and in change in statin use and cardiology visits (yes/no) pre- to post-screening. Results: Of 1,630 individuals (18% Black) with a baseline LDCT in 2018, moderate or severe CAC was documented in 154 (9.4%). Moderate or severe CAC prevalence was significantly higher among Black versus Non-Black ( 17.7 % vs 7.1%; p= &amp;lt;0.001) individuals and men versus women ( 11.7% vs 7.1%; p=0.002 ). Pre- to post-LCS increases in statin use (68.2% vs. 76.0%; p=0.02) and cardiology visits (25.9% vs. 50.7%; p&amp;lt;0.01) were observed, overall. Statin use did not differ by race, sex, or race-sex group in the pre- or post- periods. Cardiology visits were less common among Blacks (18.2% vs. 28.9%; p=0.14) and women ( 18.2% vs. 28.9%; p= 0.14) in the pre-LCS period with Black women (8.3%) being the least likely to have a cardiology visit before LCS. Post-LCS, the cardiology gap between Black and Non-Black individuals (43.6% vs. 55.6%: p=0.16) narrowed and was eliminated between women and men (53.6 % vs. 50%; p=0.67). This was due in part to a substantial uptick of cardiology visits post-LCS in Black females. However, Black men, were significantly less likely than Non-Black men (32.3 % vs 56.7% ; p=0.024 ) and Black women (32.2% vs. 62.5%; p=0.024) to have a cardiology visit post-LCS . Conclusions: Our study is on-going; however, preliminary results suggest that in addition to reducing lung cancer mortality, LCS provides an opportunity for CAC detection and its related management. LCS, if implemented equitably with comprehensive follow-up of incidental findings, may help to close gaps in cardiac care for Black individuals and women. Further investigation is needed to assess whether appropriate follow-up of CAC decreases cardiovascular risks for those undergoing screening. Citation Format: Christine Neslund-Dudas, Katie R. Zarins, Punith Shetty, Andrea E. Cassidy-Bushrow, Nada Al-Antary, Katie A. Latack, Vritti Gupta, Michael Simoff, Riley Draper, Samuel Wilcox, Kendra Worden, Kathy LaRaia, Kelly Hirko. Follow-up of moderate and severe coronary artery calcifications identified on lung cancer screening CT scans: An opportunity to improve cardiac health outcomes in Black men and women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C121.

Beyond the Cardiovascular Effects of Glucagon-like Peptide-1 Receptor Agonists: Body Slimming and Plaque Stabilization. Are New Statins Born?

Atherosclerosis is a chronic inflammatory disease characterized by lipid and inflammatory cell deposits in the inner layer of large- and medium-sized elastic and muscular arteries. Diabetes mellitus (DM) significantly increases the risk of cardiovascular diseases and the overall and cardiovascular mortality, and it is a pro-atherogenic factor that induces atherosclerosis development and/or accelerates its progression through a multifactorial process. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of drugs, belonging to the armamentarium to fight type 2 DM, that have shown robust reductions in atherosclerotic events and all-cause mortality in all studies. Preclinical studies have shown that GLP-1RAs play a role in the immunomodulation of atherosclerosis, affecting multiple pathways involved in plaque development and progression. In this review, we wanted to explore the translational power of such preclinical studies by analyzing the most recent clinical trials investigating the atheroprotective effect of GLP-1RAs.

Effect of timely availability of TTR-stabilizing therapy on diagnosis, treatment initiation, and cardiovascular outcomes in transthyretin amyloid cardiomyopathy

Abstract Background Transthyretin-stabilization reduces cardiovascular morbidity and mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Despite increased access, regional differences in the availability of therapy continue to exist, and how these may affect diagnostic efficacy and cardiovascular outcomes is currently unknown. Objective To determine how access to and availability of tafamidis affected time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in patients with ATTR-CM. Methods and Results 91 consecutive patients diagnosed with ATTR-CM between June 2019 and June 2021 were evaluated for TTR-stabilizing therapy with tafamidis. Access was regulated by an expanded access program for the initial 42 patients (early cohort; 46.2%), while insurance coverage was required for the latter 49 patients (facilitated access cohort, 53.8%) after local regulatory drug approval in April 2020. Tafamidis was started in 37 of 42 (88.1%), and 43 of 49 patients (87.8%), respectively. Baseline characteristics, e.g., age (76.3±6.4 vs. 77.3±6, p = 0.45), sex (male: 95.2% vs. 93.9%) and ATTR-CM disease stage (≤stage 2: 88.2% vs. 90.9%, p= 0.919) were comparable between both groups. Timely availability of tafamidis after April 2020 numerically reduced time from first presentation to diagnosis (median [months (IQR)]) from 6.2 (1.3;28.9) to 2.4 (0.7; 21.7) months (p = 0.196) and from presentation to therapy from 24.4 (10.7;46.8) to 11.8 (6.4; 32.4) months (p = 0.127). While RV function assessed by echocardiography significantly decreased in the early cohort between diagnosis and therapy initiation (S’ velocity 10±2.2 to 9.2±2.2 cm/s; p = 0.018; TAPSE 17.3±4.7 to 15.7±3.9, p = 0.008) it remained stable in the facilitated access cohort (S’ velocity 9.56±2.57 to 9.36±2.28 cm/s; p = 0.83; TAPSE 15.6±4.2 to 16.3±3.1, p = 0.45). After a median follow-up 42.3 and 24.9 months in the early and facilitated access cohort, respectively, timely availability of tafamidis in the facilitated access cohort was associated with a significant reduction of annual heart failure hospitalisations (treated: 0.12±0.34 vs. 0.5±1, p = 0.049; overall cohort: 0.17±0.37 vs. 0.35±0.47, p = 0.044). Overall, timely diagnosis of ATTR-CM within 12 months of first presentation was associated with a significant reduction in all-cause mortality [HR = 3.490 (95% CI 1.37 to 8.91), p = 0.009], prolonged survival without MACE [HR = 2.50 (95% CI 1.30 to 4.81), p = 0.006] or heart failure hospitalisation [HR = 2.52 (95% CI 1.24 to 5.16), p = 0.011]. Conclusions Availability of tafamidis numerically shortened time-to-diagnosis and time-to-therapy initiation in ATTR-CM patients. Timely diagnosis and initiation of therapy was associated with a reduction in all-cause mortality and heart failure hospitalisations.Door-to-diagnosis-therapyClinical outcomes

A national heart failure initiative is associated with improved use of quadruple guideline-directed medical therapy

Abstract Background Heart Failure (HF) is projected to impact over 8 million people in the US by 2030. The 2022 AHA/ACC/HFSA Guideline for the Management of HF recommend four foundational medication classes for treating HFrEF patients: RAAS inhibitors, preferably angiotensin receptor/neprilysin inhibitor (ARNi), evidence-based beta-blockers (EBBB), sodium-glucose cotransporter-2 inhibitor (SGLT2i) and mineralocorticoid receptor antagonist (MRA) referred to as Quadruple Guideline-Directed Medical Therapy (Q-GDMT). Q-GDMT has shown an estimated 73% relative and 26% absolute reduction in all-cause mortality over 2 years. Yet, despite remarkable clinical potential, these therapies are patently underutilized in clinical practice. It is unknown whether an implementation science strategy may enhance adherence to Q-GDMT for HF. Methods IMPLEMENT-HF (IHF) is a national HF quality improvement initiative composed of a multidisciplinary learning collaborative and resource repository across seven U.S regions. IHF promotes adherence to Q-GDMT by focusing on early adoption and rapid adherence to prescribing at hospital discharge and within 30 days post discharge. Multi-disciplinary participation in the learning collaborative includes pharmacy, provider groups, nursing, quality, social services, outpatient clinics and others. Shared interventions to promote Q-GDMT include formulary changes (e.g., adding SGLT2i), optimizing electronic health record tools (disease-specific order sets, dot phrases), clinician education, and user-friendly patient resources to address medication access. IHF sites receive educational materials, including webinars, learning modules, pocket guideline booklets, and reminder cards to reinforce Q-GDMT. IHF participating hospitals collect Q-GDMT data at discharge and at 30 days post discharge in Get With The Guidelines®-Heart Failure (GWTG-HF). These data were analyzed from baseline (Q1 Q2 2021 aggregate) through Q3 2022. Results Data from 71 IHF participating sites of 13,858 HFrEF patient hospitalization episodes (median age 69, 34% females, median LVEF 24%), demonstrated Q-GDMT prescription at discharge increased from 14% at baseline to 47% in Q3 2022 (p value &amp;lt;0.001). 30-day post discharge data from 52 IHF sites demonstrated an increase in Q-GDMT from 9% at baseline to 58% in Q3 2022 (p value &amp;lt;0.001) as seen in Figure 1. Conclusions Among sites participating in IHF, the use of an implementation science strategy suggest a rapid increase in prescribing Q-GDMT for eligible HFrEF patients at discharge and 30-days post discharge. This multi-region quality improvement initiative demonstrates the potential for this learning collaborative model to drive improvement in adherence to Q-GDMT prescribing, using shared implementation strategies to overcome barriers. Ongoing study will assess continued compliance and clinical outcomes with Q-GDMT beyond the timeframe of this analysis.Quadruple Medication Therapy baseline-Q3

Intracoronary imaging guided percutaneous coronary intervention of stent restenosis: does it make a difference?

Abstract Background In-stent restenosis (ISR) remains the most common cause of stent failure after percutaneous coronary intervention (PCI). Compared to coronary angiography (CA), intracoronary imaging (ICI) provides a more accurate and detailed characterization of the degree of ISR and may help identify the underlying pathophysiological mechanism. Although recommended in the European guidelines, the impact of ICI in clinical outcomes in ISR is still under discussion. Purpose Our study aimed to analyze and compare clinical outcomes between CA PCI (group 1 - G1) and ICI-guided PCI (Intravascular ultrasound (IVUS) or optical coherence tomography (OCT)) (group 2 - G2). Methods We performed a retrospective single-center review of all consecutive patients with ISR treated in our center from September 2014 to January 2022. Patients with acute stent thrombosis were excluded. Primary endpoint was defined as death by all causes and secondary endpoint as a composite of cardiovascular (CV) mortality, culprit ISR PCI and ischemic stroke. Results 130 patients were included (mean age 66.23 ± 11.832 years, 77.7% male and mean follow-up period (FUP) 48.70 ± 27.356 months). Mean left ventricular ejection fraction was 50.19 ± 10.509%, 66.2% had dyslipidemia, 45.3% hypertension, 38.5% diabetes, 36.2% heart failure and 29.2% previous multivessel PCI. A total of 142 ISR lesions from 136 arteries were treated and ICI was used in 37 (28.5%) patients (IVUS in 16 (12.3%) and OCT in 21 (16.2%)). The ISR coronary segment and pattern is described in Table 1. The mechanism for ISR was identified in 23 lesions. The most common indication for coronary angiography was stable angina in 34.6% and NSTEMI in 31.5% and ISR was the culprit in 128 (98.5%) of the cases. The groups were well matched regarding baseline characteristics and comorbidities. PCI strategy was more often drug-eluting stenting (DES) vs drug-coated balloon (DCB) in group 2 (DES 18.3% vs 51.4% and DCB 81.7% vs 43.2% in G1 and G2 respectively). And, as expected, treatment of bifurcation lesions was more frequent in group 2 (9.7% G1 vs 30.6% G2). During the FUP there were 10 (7.7%) CV deaths and 19 (14.6%) non-CV deaths (19 in G1 and 0 in G2). The composite outcome of CV mortality, ischemic stroke and culprit ISR PCI occurred in 19 (20.2%) patients in G1 and 1 (2.7%) patient in G2. The use of ICI was associated with reduced all-cause mortality (HR=0.667 [95% CI 0.584-0.760], p=0.011) and reduced composite outcome (B (95%CI): -0.251 (-0.455 - -0.046), p=0.017). No difference between IVUS or OCT was found. The PCI strategy (DES vs DCB), stent type, length or diameter were not predictors of outcomes. Conclusion In IRS PCI, the use of ICI compared to standard of care CA was associated with a reduction in all-cause mortality and composite outcome of CV mortality, culprit ISR PCI and ischemic stroke. The strategy of PCI differed with DES being used more frequently than DCB. No difference between IVUS or OCT was found.

Left appendage closure after intracranial hemorrhage: safety, efficacy and timing

Abstract Background Oral anticoagulation (OAC) use increases the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF). Left atrial appendage occlusion (LAAO) is an alternative to OAC, however data about its use in patients with prior ICH is scare and the timing of its performance is controversial. Furthermore, the long-term outcomes in this group of patients have not been described. Objective To evaluate the safety and efficacy of LAAO in patients with non-valvular AF and prior ICH (CHA2SVASc &amp;gt;2) and to determine adequate timing of its performance. Methods The sample was obtained from a cohort of 397 patients with AF in which LAAO was performed between 2009 and 2020. In 115 of these patients, the indication for this procedure was ICH (29.8 %). Patients were divided into two groups: early occlusion (n=68; 59%), in which the procedure was performed before 90 days had elapsed after the bleeding, and late occlusion (n=47; 41%), after 90 days. Results Procedure success was 97% globally. Annual incidence of ischemic events was of 0,6%, with an absolute risk reduction of 5,9% and relative risk reduction of 90,3% compared to the predicted risk by CHA2DS2-VASC score. Regarding major hemorrhagic events, annual incidence was of 4%, with an absolute risk reduction of 3,4% and relative risk reduction of 45% compared to the predicted risk by HASBLED score. There were no significant differences between the procedures performed in patients with history of intracranial bleeding and other indications for the procedure. Early closure (first 90 days after the intracranial hemorrhage) was as safe as late closure, without an increase in in-hospital bleedings or complications. Furthermore, long-term follow-up demonstrated a significant reduction in all-cause mortality (11.76% versus 46.8%; HR 0.2, IC95% 0.07-0.55; p&amp;lt;0.001). compared with late occlusion. Conclusions Left atrial appendage occlusion is an effective and safe treatment option to reduce the risk of ischemic stroke in selected patients with AF patients and history of ICH over mean follow-up of 3 years. Early occlusion seems to be at least as safe and effective as late occlusion and therefore could potentially reduce the rate of complications after ICH in selected patients.Survival and closure timingIschemic and bleeding risk reduction

Mortality benefit of implantable cardioverter-defibrillators for primary prevention of sudden cardiac death: a real-world analysis

Abstract Background Nearly 1,000 people suffer an out-of-hospital sudden cardiac arrest daily in the United States, with only 10% surviving when treated by emergency medical services. Implantable cardioverter-defibrillators (ICDs) are a proven first-line treatment in limiting sudden cardiac death, but the evidence has become dated. We sought to assess the survival benefit of ICDs in a contemporary population. Purpose Using a real-world database, we aimed to determine the current impact of ICDs on mortality in primary prevention patients. Methods Data were obtained from a de-identified electronic health record database. We included patients that met ICD primary prevention indication (PPI) implantation criteria between 2012 and 2019, had one year of available data before the PPI, and survived for at least one year post-PPI. Patients were split into 2 groups based on ICD implant status (implanted vs not implanted) within one year after PPI. The primary endpoint was the overall mortality rate, beginning at one-year post-PPI. Propensity matching was performed to account for baseline differences between patients that did and did not receive an ICD, and all-cause mortality rates were compared using the Kaplan-Meier method and Cox proportional hazard model. Results A total of 25,296 patients were identified as having a PPI for ICD implantation, of which 2,118 (8.4%) were implanted with an ICD within a year. Implanted patients were younger than non-implanted patients (63.4 vs 66.1 years) and had a smaller proportion of females (25.0% vs 36.7%). After 4 to 1 propensity matching, patients who did not have an ICD implanted had a mean age of 63.6 years and were 25.1% female. In the matched cohort, the 5-year all-cause mortality rate was 37.6% (CI: 33.2%-41.7%) in PPI patients who received an ICD and 44.9% (CI: 42.8%-47.0%) in those that did not receive an ICD. A Cox proportional hazard model revealed a 25.3% lower risk of all-cause mortality in PPI patients implanted with an ICD compared to PPI patients without an ICD (HR: 0.747; CI: 0.670-0.834; p&amp;lt;0.001 [Figure 1]). Conclusion In a large cohort of PPI patients that survived at least one year after indication, those implanted with an ICD during that year had a 25.3% lower risk of all-cause mortality than similar patients who did not receive an ICD, consistent with landmark trials. Thus, ICD implantation continues to be associated with a reduction in all-cause mortality in PPI patients at risk for sudden cardiac death.

Impact of intracoronary imaging-guided percutaneous coronary intervention on procedural outcomes among patients with cardiogenic shock

Abstract Background Intracoronary imaging (ICI), including intravascular ultrasound (IVUS) or optical coherence tomography (OCT), is known to correlate with a reduction in rates of cardiac death after percutaneous coronary intervention (PCI), driven by lower rates of reinfarction and stent thrombosis. [1,2] However, there are limited data around its utility amongst patients with acute coronary syndrome (ACS) and cardiogenic shock, who are inherently at a high risk of stent thrombosis. Aims To examine the frequency of utilisation of ICI among ACS patients with cardiogenic shock, and their subsequent outcomes, in a national cohort of PCI procedures over a six-year period. Methods All PCI procedures for ACS patients with cardiogenic shock in England and Wales between 2014 and 2020 were retrospectively analysed, stratified into two groups: ICI and non-ICI groups. Multivariable logistic regression analyses were performed to examine the odds of in-hospital major adverse cardiovascular and cerebrovascular events (MACCE; composite of all-cause mortality, acute stroke/transient ischaemic attack (TIA), and reinfarction) and major bleeding (BARC 3-5) in the ICI-guided group, compared with the non-ICI group, as well as predictors of receipt of ICI-guided PCI. Results Of 15,738 PCI procedures performed between 2014 and 2020, 1,240 procedures (7.9%) were ICI-guided. Overall, the rate of ICI use amongst those with cardiogenic shock has more than doubled from 2014 (5.7%) to 2020 (13.3%). The ICI-guided group were predominantly younger, males, with a higher proportion of non-ST elevation ACS and stent thrombosis. The rate of MACCE was significantly lower in the ICI-guided group compared with the non-ICI group (29.8% vs. 38.2%, p&amp;lt;0.001), driven by lower rate of all-cause mortality (28.6% vs. 37.0%, p&amp;lt;0.001). (Figure 1) There were no differences for other secondary outcomes between groups. In multivariable analysis, the odds of MACCE and all-cause mortality in those undergoing ICI-guided PCI remained significantly lower than in the non-ICI group (OR 0.65 95% CI 0.56, 0.76 and OR 0.65 95% CI 0.55, 0.75, respectively, p&amp;lt;0.001 for both). (Figure 2). Advanced age (OR 0.98) and STEMI presentation (OR 0.54) negatively correlated with ICI use while stent thrombosis presentation (OR 2.66), previous PCI (OR 2.02), intervention on LMS (OR 4.19) and proximal LAD lesions (OR 1.62) and need for calcium modification (OR 2.13) positively correlated with increased ICI use. Conclusion The utilisation of ICI among patients with cardiogenic shock has more than doubled over a 6-year period on a national level but remains significantly under-utilised, with less than 1-in-6 patients in receipt of ICI-guided PCI in 2020. ICI use is associated with a prognostic benefit in terms of reduction of in-hospital MACCE and all-cause mortality in this high-risk patient group and should be more frequently utilised to increase their long-term survival.Figure 1.In-hospital crude outcomesFigure 1B.Adjusted odds ratios (OR)

Real world prognostic impact and predictors of adherence to statin therapy after STEMI on first year follow up: results from the FAST STEMI registry

Abstract Background The impact of statin therapy on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in real-world patients is understudied. Purpose The aim of this study was to identify predictors of low compliance to statin therapy and estimate its impact on cardiovascular (CV) outcomes and mortality in the first year after the index event. Methods We evaluated real-world adherence to the most common cardiovascular drugs by comparing the number of bought tablets in drugstores to the expected tablets at 1 year and on total follow-up length. A total amount of 6043 patients from 2012 to 2017 was enrolled in the FAST STEMI registry and followed up for 4,7±1,6 years; 299 patients with intraprocedural and intrahospital deaths were excluded. The main outcomes evaluated were all-cause death, cardiovascular death, myocardial infarction, major and minor bleeding events and ischemic stroke. The best compliance cut-off was found by ROC curve analysis with Youden index; Kaplan Meier and Cox proportional hazard models were performed to evaluate cumulative event rates of cardiovascular mortality at follow-up. Predictors of lower adherence were evaluated at univariate and multivariate analysis with logistic regression. Results From a total of 5744 patients 4333 were men (75,4%) with an average age of 64,7±12,5 years old; 699 (2,2%) were diabetic, 311 (5,4%) presented with severe chronic kidney disease (CKD) while 237 (4,1%) had previous ischemic cardiopathy disease. Mean statin adherence was 89,9% (IQR 41,1 – 100): after univariate and multivariate analysis age≥75 (OR 0.597, IC 0.514-0.692), previous ischemic stroke (OR 0.607, IC 0.416-0.886), known ischemic cardiopathy (OR 0.675, IC 0.503-0.904) and chronic kidney disease (OR 0.667, IC 0.552-0.879) resulted as predictors of lower compliance, whereas preserved ejection fraction (OR 1.282, IC 1.133-1.457) resulted predictor of adequate adherence to statin therapy. Statin adherence upper than 49.05% (identified at Youden’s analysis as best cut-off) reduced both cardiovascular (0,3% vs. 6,8%; HR 0.33; 95%CI 0.18-0.59; p = 0,001) and all-cause mortality (0,7% vs 18,1%, HR 0,22, 95%CI 0.15-0.37, p&amp;lt;0.001). Regarding cardiovascular outcomes, statin optimal adherence reduced ischemic stroke incidence (1% vs 2,5%, p=0.001) while there was no difference on the number of myocardial infarctions nor hemorrhagic events at 1-year follow up. Conclusions In the real-world setting, statin adherence after STEMI was independently associated to a reduction of cardiovascular mortality, all-cause mortality and ischemic stroke incidence at 1-year follow-up. Elderly age, previous ischemic stroke, known ischemic cardiopathy and CKD resulted as independent predictors of lower compliance to statin therapy.CV and all-cause mortalityCox regression on CV mortality at 1-year

The effectiveness of eplerenone vs spironolactone on left ventricular systolic function, hospitalization and cardiovascular death in patients with chronic heart failure - HFrEF

Abstract Background Heart failure remains one of the most prevalent clinical syndromes associated with significant morbidity and mortality. According to current guidelines MRA are recommended to reduce the risk of HF hospitalization and death in all patients with symptomatic heart failure. Purpose The aim of our study was to determine the efficacy of eplerenone vs. spironolactone on left ventricular systolic function (LVEF) in patients with chronic heart failure, especially their effect on preventing hospitalization, reducing mortality, and improving clinical status among patients with chronic HF. Methods From June 2021 to June 2022, the study was a randomized, prospective clinical trial single blind study. A total of 142 patients of chronic heart failure with reduced ejection fraction were selected by random sampling. Each patient was randomly allocated into either of the two groups and was continued receiving treatment with either spironolactone (Spiron-HF group) or eplerenone (Epler-HF group). Patients in Epler-HF group were compared with an arm of the same size. Each patient was evaluated clinically and echocardiographically at the beginning of treatment, after 6 months and at the end of 12th month. Results After 12 months of treatment, significant improvement of left ventricular ejection fraction was observed in eplerenone treated arm (37.9 ± 3.8 ± 4.6 in Spiron-HF group versus 40.1 ± 5.7 in Epler-HF group; P &amp;lt; 0.05). A significant reduction in left ventricular end-systolic volume (6.3 ± 2.5ml in Spiron-HF versus 17.8± 4.4ml in Epler-HF group; P &amp;lt; 0.05) and left ventricular systolic diameter volume (2.7 ± 0.5ml in Spiron-HF versus 6.7 ± 0.2ml in Epler-HF group; P &amp;lt; 0.05), occurred after 12 months of treatment. The effects of both MRA agents' spironolactone and eplerenone on the primary composite outcome, each of the individual mortality and hospital admission outcomes are shown in Figure 1 and 2. Patients of the Epler-HF group showed statistically significant lower cardiovascular mortality (HR 0.53; 95% CI 0.34–0.82; p= 0.007) and all-cause mortality (HR 0.64; 95% CI 0.44–0.93; p= 0.022) than patients of the Spiron-HF group. The statistical analysis did not show a statistically significant difference between Epler -HF and Spiron-HF study groups regarding the risk of the primary composite outcome; cardiovascular death or hospitalization due to HF (Hazard Ratio (HR) eplerenone vs. spironolactone = 0.95; 95% Confidence Interval (CI) 0.73– 1.27; p= 0.675). Conclusion Our study has demonstrated favorable effects of eplerenone on cardiac remodeling parameters and reduction of cardiovascular mortality and all-cause mortality compared with spironolactone in the treatment of HFrEF. The ability of eplerenone to effectively block the mineralocorticoid receptor while minimizing side effects and a significant reduction in the risk of hospitalization and cardiovascular death confirms its key role in the treatment of patients with chronic HFrEFCumulative estimates of cardiovascular mCumulative incidence of the primary end-