Guideline-recommended Medical Therapy Research Articles

Insights on prevalence and incidence of anemia and rapid up-titration of oral heart failure treatment from the STRONG-HF study.

Anemia is one of the most frequent comorbidities in patients with heart failure (HF), which potentially can interfere with the effect of guideline-recommended HF medical therapy and can be associated with the use of neurohormonal blockers. The aim of this analysis was to determine the prevalence and changes of anemia status in the STRONG-HF study, its association with clinical endpoints, and possible interaction of the presence of anemia with the efficacy and safety of high-intensity HF treatment. The design and main results of the study have been previously described. Patients were randomized within 2days prior to anticipated hospital discharge after HF worsening in a 1:1 fashion to either high-intensity care (HIC) or usual care (UC). Baseline characteristics, clinical and safety outcomes, and treatment effect of HIC vs. UC on the primary and secondary outcomes were compared in groups based on baseline anemia. In addition, dynamics of hemoglobin during the study follow-up and predictors of incident anemia at 90days were investigated. The proportion of anemia in 1077 STRONG-HF patients at enrollment was 27.2%, while at 90days, it changed to 32.1%. The primary composite outcome occurred in 18.2% of patients without baseline anemia, and 22.5% of patients with baseline anemia (unadjusted HR 1.27; 95% CI 0.90-1.80), a difference that did not reach statistical significance. However, patients with baseline anemia had significantly less improvement of EQ-VAS questionnaire values from baseline to day 90 (adjusted LS-Mean difference -2.34 (-4.37, -0.31), P = 0.02). During the study, anemia developed in 19.4 and 14.6% in HIC and UC groups, respectively. The opposite phenomenon-recovery of anemia-occurred in 27.6 and 28.8% in HIC and UC groups (P = 0.1379). The predictors of incident anemia at 90days were male sex, geographical region other than Europe, ischemic etiology, higher glucose, and elevated uric acid at baseline. The percentages of optimal doses of renin-angiotensin system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists were not different between anemic and non-anemic patients. High-intensity care strategy did not increase rate of incident anemia at 90days and reduced the rate of primary and secondary endpoints regardless of baseline hemoglobin. Hemoglobin level and status of anemia have a dynamic nature in the acute HF patients in the post-discharge period dependent on multiple factors. High-intensity HF treatment is safe and beneficial regardless of baseline hemoglobin level and presence of anemia. The improvement of quality of life is significantly lower in anemic HF patients implying specific attention to correction of this condition.

Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation.

Whether transcatheter mitral-valve repair improves outcomes in patients with heart failure and functional mitral regurgitation is uncertain. We conducted a randomized, controlled trial involving patients with heart failure and moderate to severe functional mitral regurgitation from 30 sites in nine countries. The patients were assigned in a 1:1 ratio to either transcatheter mitral-valve repair and guideline-recommended medical therapy (device group) or medical therapy alone (control group). The three primary end points were the rate of the composite of first or recurrent hospitalization for heart failure or cardiovascular death during 24 months; the rate of first or recurrent hospitalization for heart failure during 24 months; and the change from baseline to 12 months in the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS; scores range from 0 to 100, with higher scores indicating better health status). A total of 505 patients underwent randomization: 250 were assigned to the device group and 255 to the control group. At 24 months, the rate of first or recurrent hospitalization for heart failure or cardiovascular death was 37.0 events per 100 patient-years in the device group and 58.9 events per 100 patient-years in the control group (rate ratio, 0.64; 95% confidence interval [CI], 0.48 to 0.85; P = 0.002). The rate of first or recurrent hospitalization for heart failure was 26.9 events per 100 patient-years in the device group and 46.6 events per 100 patient-years in the control group (rate ratio, 0.59; 95% CI, 0.42 to 0.82; P = 0.002). The KCCQ-OS score increased by a mean (±SD) of 21.6±26.9 points in the device group and 8.0±24.5 points in the control group (mean difference, 10.9 points; 95% CI, 6.8 to 15.0; P<0.001). Device-specific safety events occurred in 4 patients (1.6%). Among patients with heart failure with moderate to severe functional mitral regurgitation who received medical therapy, the addition of transcatheter mitral-valve repair led to a lower rate of first or recurrent hospitalization for heart failure or cardiovascular death and a lower rate of first or recurrent hospitalization for heart failure at 24 months and better health status at 12 months than medical therapy alone. (Funded by Abbott Laboratories; RESHAPE-HF2 ClinicalTrials.gov number, NCT02444338.).

Hypertension evaluation and management in new young patients: are we doing our female patients a disservice?

Purpose Cardiovascular disease (CVD) is one of the leading causes of death in women, largely underpinned by hypertension. Current guidelines recommend first-line therapy with a RAAS-blocking agent especially in young people. There are well documented sex disparities in CVD outcomes and management. We evaluate the management of patients with newly diagnosed hypertension in a tertiary care clinic to assess male–female differences in investigation and treatment. Methods Clinic letters of all new patients under the age of 51 attending the Glasgow Blood Pressure Clinic between January and December 2023 were reviewed. The primary outcomes measured were first-line treatment choices, deviations from guideline-recommended treatment, investigations for secondary hypertension, and documentation of female-specific risk factors and family planning advice. Secondary outcomes included clinical characteristics such as systolic and diastolic blood pressure at referral and at the new patient appointment, age at diagnosis, age at first appointment, and the number of antihypertensive drugs prescribed at referral. Results One hundred and five (59:46, M:F) new patient encounters were reviewed after sixteen exclusions for non-attendance and inappropriate clinic coding. Choice of first line antihypertensive agent did not vary between sexes with no deviation from guideline-recommended medical therapy. Men, however, had more biochemical investigations conducted for secondary causes across all ages. This was greatest in those under 40 years old. There was suboptimal documentation of female-specific risk factors (obstetric and gynaecological history), contraceptive drug history and family planning with 35%, 20%, and 15.6%, respectively. Conclusion In 2023, women under 51 years of age seen in a tertiary care hypertension clinic received similar first-line treatment to their male peers. However, relevant female-specific histories were suboptimally documented for these patients. Whilst therapeutic approaches in men and women appear to be similar in this clinic, there are opportunities to improve CVD prevention in women, even in a specialised clinic setting.

Guideline-recommended medical therapy for de novo heart failure with reduced ejection fraction: be patient waiting for reverse remodelling.

Guideline-recommended medical therapy for de novo heart failure with reduced ejection fraction: be patient waiting for reverse remodelling.

Therapy duration and improvement of ventricular function in de novo heart failure: the Heart Failure Optimization study.

In patients with de novo heart failure with reduced ejection fraction (HFrEF), improvement of left ventricular ejection fraction (LVEF) is expected to occur when started on guideline-recommended medical therapy. However, improvement may not be completed within 90 days. Patients with HFrEF and LVEF ≤ 35% prescribed a wearable cardioverter-defibrillator between 2017 and 2022 from 68 sites were enrolled, starting with a registry phase for 3 months and followed by a study phase up to 1 year. The primary endpoints were LVEF improvement > 35% between Days 90 and 180 following guideline-recommended medical therapy initiation and the percentage of target dose reached at Days 90 and 180. A total of 598 patients with de novo HFrEF [59 years (interquartile range 51-68), 27% female] entered the study phase. During the first 180 days, a significant increase in dosage of beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists was observed (P < .001). At Day 90, 46% [95% confidence interval (CI) 41%-50%] of study phase patients had LVEF improvement > 35%; 46% (95% CI 40%-52%) of those with persistently low LVEF at Day 90 had LVEF improvement > 35% by Day 180, increasing the total rate of improvement > 35% to 68% (95% CI 63%-72%). In 392 patients followed for 360 days, improvement > 35% was observed in 77% (95% CI 72%-81%) of the patients. Until Day 90, sustained ventricular tachyarrhythmias were observed in 24 wearable cardioverter-defibrillator carriers (1.8%). After 90 days, no sustained ventricular tachyarrhythmia occurred in wearable cardioverter-defibrillator carriers. Continuous optimization of guideline-recommended medical therapy for at least 180 days in HFrEF is associated with additional LVEF improvement > 35%, allowing for better decision-making regarding preventive implantable cardioverter-defibrillator therapy.

When to implant an ICD in patients with heart failure and reduced ejection fraction? Insights from the HF-OPT trial

Abstract Background In patients with de novo heart failure with reduced ejection fraction (HFrEF) improvement of left ventricular ejection fraction (LVEF) is expected to occur when started on guideline-recommended medical therapy (GRMT). However, the period of time, when LVEF improvement is completed, is unknown. Purpose Evaluation of improvement of LVEF &amp;gt;35% within the first year after de novo diagnosis of HFrEF with severely reduced LVEF &amp;lt;35%. Methods In the prospective HF-OPT-trial, patients with de novo HFrEF and LVEF ≤35% prescribed the wearable cardioverter defibrillator (WCD) were enrolled and followed up to one year. GRMT was initiated and uptitrated according current guidelines. LVEF improvement &amp;gt;35% under GRMT was echocardiographically assessed at day 0, day 90, day 180 and day 360. Results A total of 487 patients (59 years (IQR: 51-68), 27% women) were followed until day 180. Out of 487 patients 392 patients were followed additionally to day 360. Dosages of GRMT were significantly increased during follow-up (p&amp;lt;0.001) At 90 days, 46% (CI: 41%-50%) of the patients had LVEF improvement &amp;gt;35%. About half of those with persistently LVEF&amp;lt;35% at day 90 (46%, CI: 40%-52%) had LVEF improvement &amp;gt;35% by day 180, increasing the total rate of improvement &amp;gt;35% to 68% (CI: 63% - 72%). Until day 360 the rate of LVEF improvement &amp;gt;35% increased to 78%. Conclusions 78% of patients with de novo HFrEF showed improvement in LVEF &amp;gt;35% during the first year after diagnosis following GRMT. This finding impacts decision making for primary preventive ICD implantation.Development of LVEF.

Chronic remote ischemic conditioning treatment in patients with chronic stable angina (EARLY-MYO-CSA): a randomized, controlled proof-of-concept trial

BackgroundChronic remote ischemic conditioning (CRIC) has been shown to improve myocardial ischemia in experimental animal studies; however, its effectiveness in patients with chronic stable angina (CSA) has not been investigated. We conducted a proof-of-concept study to investigate the efficacy and safety of a six-month CRIC treatment in patients with CSA.MethodsThe EARLY-MYO-CSA trial was a prospective, randomized, controlled trial evaluating the CRIC treatment in patients with CSA with persistent angina pectoris despite receiving ≥ 3-month guideline-recommended optimal medical therapy. The CRIC and control groups received CRIC (at 200 mmHg) or sham CRIC (at 60 mmHg) intervention for 6 months, respectively. The primary endpoint was the 6-month change of myocardial flow reserve (MFR) on single-photon emission computed tomography. The secondary endpoints were changes in rest and stress myocardial blood flow (MBF), angina severity according to the Canadian Cardiovascular Society (CCS) classification, the Seattle Angina Questionnaire (SAQ), and a 6-min walk test (6-MWT).ResultsAmong 220 randomized CSA patients, 208 (105 in the CRIC group, and 103 in the control group) completed the treatment and endpoint assessments. The mean change in MFR was significantly greater in the CRIC group than in the control group (0.27 ± 0.38 vs. − 0.04 ± 0.25; P < 0.001). MFR increased from 1.33 ± 0.48 at baseline to 1.61 ± 0.53 (P < 0.001) in the CRIC group; however, a similar increase was not seen in the control group (1.35 ± 0.45 at baseline and 1.31 ± 0.44 at follow-up, P = 0.757). CRIC treatment, when compared with controls, demonstrated improvements in angina symptoms assessed by CCS classification (60.0% vs. 14.6%, P < 0.001), all SAQ dimensions scores (P < 0.001), and 6-MWT distances (440 [400–523] vs. 420 [330–475] m, P = 0.016). The incidence of major adverse cardiovascular events was similar between the groups.ConclusionsCSA patients benefit from 6-month CRIC treatment with improvements in MFR, angina symptoms, and exercise performance. This treatment is well-tolerated and can be recommended for symptom relief in this clinical population.Trial registration[chictr.org.cn], identifier [ChiCTR2000038649].

NT-proBNP and high intensity care for acute heart failure: the STRONG-HF trial.

STRONG-HF showed that rapid up-titration of guideline-recommended medical therapy (GRMT), in a high intensity care (HIC) strategy, was associated with better outcomes compared with usual care. The aim of this study was to assess the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and its changes early during up-titration. A total of 1077 patients hospitalized for acute heart failure (HF) and with a >10% NT-proBNP decrease from screening (i.e. admission) to randomization (i.e. pre-discharge), were included. Patients in HIC were stratified by further NT-proBNP changes, from randomization to 1 week later, as decreased (≥30%), stable (<30% decrease to ≤10% increase), or increased (>10%). The primary endpoint was 180-day HF readmission or death. The effect of HIC vs. usual care was independent of baseline NT-proBNP. Patients in the HIC group with stable or increased NT-proBNP were older, with more severe acute HF and worse renal and liver function. Per protocol, patients with increased NT-proBNP received more diuretics and were up-titrated more slowly during the first weeks after discharge. However, by 6 months, they reached 70.4% optimal GRMT doses, compared with 80.3% for those with NT-proBNP decrease. As a result, the primary endpoint at 60 and 90 days occurred in 8.3% and 11.1% of patients with increased NT-proBNP vs. 2.2% and 4.0% in those with decreased NT-proBNP (P = 0.039 and P = 0.045, respectively). However, no difference in outcome was found at 180 days (13.5% vs. 13.2%; P = 0.93). Among patients with acute HF enrolled in STRONG-HF, HIC reduced 180-day HF readmission or death regardless of baseline NT-proBNP. GRMT up-titration early post-discharge, utilizing increased NT-proBNP as guidance to increase diuretic therapy and reduce the GRMT up-titration rate, resulted in the same 180-day outcomes regardless of early post-discharge NT-proBNP change.

Meta-Analysis on Drug and Device Therapy of New York Heart Association Functional Class IV Heart Failure With Reduced Ejection Fraction

Heart failure with reduced ejection fraction (HFrEF) is associated with significant morbidity and mortality, particularly in patients with New York Heart Association (NYHA) functional class IV symptoms. Decades of discovery have heralded significant advancements in the pharmacologic management of HFrEF. However, patients with NYHA IV symptoms remain an under-represented population in almost every clinical trial to date, leaving clinicians with limited evidence with which to guide drug treatment decisions in this patient group with severe heart failure. Randomized controlled trials of adult patients with NYHA IV symptoms of HFrEF randomized to current guideline-recommended medical therapy were included in this systematic review and meta-analysis. The outcomes of interest included the rate of all-cause mortality, cardiovascular mortality, and heart failure hospitalization. A total of 39 randomized controlled trials were included. A total of 6 studies examined angiotensin converting enzyme inhibitors, with meta-analyses of 2 demonstrating a reduced risk of all-cause mortality (relative risk (RR) 0.76, 95% confidence interval 0.59 to 0.97, p=0.03). A total of 11 studies examined β blockers, with meta-analysis of 6 demonstrating a reduced risk of all-cause mortality (risk ratio 0.74, 95% confidence interval 0.60 to 0.92, p=0.008). A study examined the mineralocorticoid antagonist spironolactone, reporting a reduced risk of all-cause mortality in the NYHA IV subgroup. A total of 6 studies examined device therapy, demonstrating the benefit of cardiac resynchronization therapy with or without an implantable cardiac defibrillator in reducing hospitalization in the NYHA IV subgroup. Although trial evidence exists for angiotensin converting enzyme inhibitors, β-blockers, and mineralocorticoid antagonist therapy in the NYHA IV population, the role of angiotensin receptor blockers is unclear. Ivabradine, angiotensin receptor neprilysin inhibitors, and sodium-glucose transport protein 2 inhibitors remain underinvestigated and have not been proved to provide any benefit above standard heart failure therapy in patients with HFrEF and NYHA IV symptoms.

Abstract 14375: Guideline Directed Medical Therapy After Peripheral Vascular Intervention and Association With Long-Term Outcomes at an Academic Health System

Introduction: Guideline-recommended medical therapy (GDMT) for cardiovascular risk reduction remains sub-optimally prescribed in patients with peripheral artery disease (PAD). To begin addressing this issue, it is key as a health system to be able to monitor electronic health record (EHR)-based real-world data to assess GDMT usage rates and its association with long-term mortality and amputation. Methods: We included all patients with PAD who underwent peripheral vascular interventions (PVI) across the Yale New Haven Health System in 2016-2022. GDMT at PVI discharge was defined as having all 3 of: angiotensin converting enzyme inhibitor/angiotensin receptor blocker (if hypertensive), antiplatelet, and statin. Propensity scores were calculated based on age, sex, race, ethnicity, and Elixhauser comorbidities. Inverse probability weighted Cox regression models with a random effect for site and provider were constructed to evaluate the relationship between GDMT and 2-year mortality and major amputation. Results: A total of 3,741 patients with PAD underwent PVI. The average age was 72.3 (± 12.9) years, and 39% were female. GDMT rates at PVI discharge ranged from 24% to 40% during the study period. Lack of GDMT at discharge had a statistically insignificant association 2-year mortality risk (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.98-1.50, p=0.07; figure top) and a significant positive association with 2-year major amputation risk (HR: 2.73, 95% CI:1.51-4.94, p&lt;0.001; figure bottom). Conclusions: This study leveraged system-wide EHR data to study GDMT use and its association with mortality and major amputation, which may serve as a metric for quality of PAD care.

Abstract 12873: Arrhythmogenic and Ischemic Cardiopathy Mimics Covid-19 Myocarditis

A 63-year-old man with a history of hypertension, hyperlipidemia and severe COVID-19 3 months earlier presented with NYHA class III-IV heart failure (HF) and intermittent claudication. Three months before, patient noted increasing dyspnea. SARS-CoV2 was verified. CT scan showed pneumonia; the severity of disease required dexamethasone and tocilizumab. Atrial fibrillation (AF) and LV EF 30% were first detected. CT scan disclosed left atrial appendage (LAA) thrombosis. Despite anticoagulants, 3 weeks later the patient developed lower limbs ischemia. Ultrasound and CT scan showed multiple thrombosis in the abdominal aorta and lower limbs arteries (Figure A). Surgery for limb ischemia was not performed due to a further decrease of LV EF to 18%. At that point, diagnosis was SARSCoV2-induced myocarditis. Нe visited our hospital for second opinion. ECG showed AF with mean heart rate (HR) of 158/min (B). Careful history collection suggested a longer AF duration which was missed and untreated due to lockdown. CRP, troponin were normal. NT-proBNP was 9326 pg/ml. After strict rate control was achieved, LV EF became 23%. Cardiac MRI with delayed gadolinium contrast revealed no fibrosis or active myocarditis (C). Angiography showed stenosis &gt;70% of the left anterior descending artery (D). After PCI, LV EF became 27%. The patient was discharged on guideline-recommended optimal medical therapy. Three months later LV EF became 30%, six months later - 47%. Thrombus in LAA was dissolved. Pulmonary vein isolation and cardioversion were performed. One week later LV EF was 60%. Currently, the patient has stable sinus rhythm and no signs of HF for &gt; 6 months. Thus, COVID-19 could contribute to the progression of atherosclerosis, modify the substrate and aggravate the severity of AF, but it was not the only cause of a serious illness in the patient. COVID-19 also had an indirect negative impact - delay the detection of cardiac pathology and cause its underdiagnosis under the guise of "post-COVID".

Female Sex is Associated with More Reinterventions after Endovascular and Open Interventions for Intermittent Claudication

Intermittent claudication (IC) is a commonly treated vascular condition. Patient sex has been shown to influence outcomes of interventions for other vascular disorders; however, whether outcomes of interventions for IC vary by sex is unclear. We sought to assess the association of patient sex with outcomes after IC interventions. The Vascular Quality Initiative was queried from 2010-2020 for all peripheral endovascular interventions (PVI), infra-inguinal bypasses (IIB), and supra-inguinal bypasses (SIB) for any degree IC. Univariable and multivariable analyses compared peri-operative and long-term outcomes by patient sex. There were 24,701 female and 40,051 male patients undergoing PVI, 2,789 female and 6,525 male patients undergoing IIB, and 1,695 female and 2,370 male patients undergoing SIB for IC. Guideline-recommended pre-operative medical therapy differed with female patients less often prescribed aspirin for PVI (73.4% vs. 77.3%), IIB (71.5% vs. 74.8%), and SIB (70.9% vs. 74.3%) or statins for PVI (71.8% vs. 76.7%) and IIB (73.1% vs. 76.0%) (all P<0.05). Female compared with male patients had lower 1-year reintervention-free survival after PVI (84.4%±0.3% vs. 86.3%±0.2%, P<0.001), IIB (79.0%±0.9% vs. 81.2%±0.6%, P=0.04), and SIB (89.4%±0.9% vs. 92.6%±0.7%, P=0.005), but similar amputation-free survival and survival across all procedures. Multivariable analysis confirmed that female sex was associated with increased 1-year reintervention for PVI (HR 1.16, 95% CI 1.09-1.24, P<0.001), IIB, (HR 1.16, 95% CI 1.03-1.31, P=0.02), and SIB (HR 1.60, 95% CI 1.20-2.13, P=0.001). Female patients undergoing interventions for IC were less often pre-operatively medically optimized than male patients, though the difference was small. Furthermore, female sex was associated with more reinterventions after interventions. Interventionists treating female patients should increase their efforts to maximize medical therapy. Future research should clarify reasons for poorer intervention durability in female patients.

Global disparities in prescription of guideline-recommended drugs for heart failure with reduced ejection fraction.

Heart failure (HF) is a global challenge, with lower- and middle-income countries (LMICs) carrying a large share of the burden. Treatment for HF with reduced ejection fraction (HFrEF) improves survival but is often underused. Economic factors might have an important effect on the use of medicines. This analysis assessed prescription rates and doses of renin-angiotensin system (RAS) inhibitors, β-blockers, and mineralocorticoid receptor antagonists at discharge and 6-month follow-up in 8669 patients with HFrEF (1458 from low-, 3363 from middle-, and 3848 from high-income countries) hospitalized for acute HF in 44 countries in the prospective REPORT-HF study. We investigated determinants of guideline-recommended treatments and their association with 1-year mortality, correcting for treatment indication bias.Only 37% of patients at discharge and 34% of survivors at 6 months were on all three medication classes, with lower proportions in LMICs than high-income countries (19 vs. 41% at discharge and 15 vs. 37% at 6 months). Women and patients without health insurance, or from LMICs, or without a scheduled medical follow-up within 6 months of discharge were least likely to be on guideline-recommended medical therapy at target doses, independent of confounders. Being on ≥50% of guideline-recommended doses of RAS inhibitors, and β-blockers were independently associated with better 1-year survival, regardless of country income level. Patients with HFrEF in LMICs are less likely to receive guideline-recommended drugs at target doses. Improved access to medications and medical care could reduce international disparities in outcome.

A multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy of immunosuppression in biopsy-proven virus-negative myocarditis or inflammatory cardiomyopathy (IMPROVE-MC).

Myocarditis is frequently associated with poor prognosis as there is no evidence-based treatment. Therefore, current international recommendations indicate that a well-designed prospective trial to confirm benefits from immunosuppressive therapy is highly warranted. The aim of the IMPROVE-MC study is to assess the efficacy and safety of immunosuppressive treatment compared with placebo on top of the guideline-recommended medical therapy in patients with biopsy-proven virus-negative myocarditis/inflammatory cardiomyopathy. The IMPROVE-MC (ClinicalTrials.gov: NCT04654988) is a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial that will recruit 100 adults, with biopsy-proven myocarditis/inflammatory cardiomyopathy, with left ventricular ejection fraction (LVEF) ≤ 45% and ≥ 3-month history of symptoms. Patients will be randomized (1:1 ratio) to a group treated with prednisone and azathioprine vs. placebo. Patients will undergo 1-year double-blind therapy followed by a 1-year observation period to assess the long-term effects of the treatment. Apart from a routine clinical work-up, all patients will undergo cardiac magnetic resonance (CMR) and biopsy during screening and 1 year after applying the therapy. Primary endpoint is a change from baseline in LVEF at 12 months. Secondary endpoints are related to clinical evaluation (including New York Heart Association class, distance in 6-minute walk test, number of patients with the need for hospitalization), laboratory findings (biomarkers of fibrosis and myocardial necrosis, concentration of anti-heart auto-antibodies, heart tissue immunohistologic assessment), diagnostic tools (e.g., changes of echocardiographic, CMR and Holter-ECG parameters) and quality of life. The IMPROVE-MC study will provide high-quality scientific data on the efficacy and safety of immunosuppressive therapy for patients with biopsy-proven myocarditis. Trial registration number and date of registration: ClinicalTrials.gov:NCT04654988; 04/12/2020.

Clinical impact of changes in mitral regurgitation severity after medical therapy optimization in heart failure

BackgroundFew data are available regarding changes in mitral regurgitation (MR) severity with guideline-recommended medical therapy (GRMT) in heart failure (HF). Our aim was to evaluate the evolution and impact of MR after GRMT in the Biology study to Tailored treatment in chronic heart failure (BIOSTAT-CHF).MethodsA retrospective post-hoc analysis was performed on HF patients from BIOSTAT-CHF with available data on MR status at baseline and at 9-month follow-up after GRMT optimization. The primary endpoint was a composite of all-cause death or HF hospitalization.ResultsAmong 1022 patients with data at both time-points, 462 (45.2%) had moderate-severe MR at baseline and 360 (35.2%) had it at 9-month follow-up. Regression of moderate-severe MR from baseline to 9 months occurred in 192/462 patients (41.6%) and worsening from baseline to moderate-severe MR at 9 months occurred in 90/560 patients (16.1%). The presence of moderate-severe MR at 9 months, independent from baseline severity, was associated with an increased risk of the primary endpoint (unadjusted hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.57–2.63; p < 0.001), also after adjusting for the BIOSTAT-CHF risk-prediction model (adjusted HR, 1.85; 95% CI 1.43–2.39; p < 0.001). Younger age, LVEF ≥ 50% and treatment with higher ACEi/ARB doses were associated with a lower likelihood of persistence of moderate-severe MR at 9 months, whereas older age was the only predictor of worsening MR.ConclusionsAmong patients with HF undergoing GRMT optimization, ACEi/ARB up-titration and HFpEF were associated with MR improvement, and the presence of moderate-severe MR after GRMT was associated with worse outcome.Graphical abstract

Cost-effectiveness of transcatheter edge-to-edge repair in secondary mitral regurgitation

BackgroundTranscatheter edge-to-edge mitral valve repair (TMVr) improves symptoms and survival for patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and severe secondary mitral regurgitation despite guideline-recommended medical...

Worse outcomes of ACS patients without versus with traditional cardiovascular risk factors

IntroductionUp to 20% of patients presenting with acute coronary syndrome (ACS) have no traditional cardiovascular risk-factors (RFs). Data regarding the determinants, management, and outcomes of these patients are scarce. ObjectivesTo evaluate the management, outcomes, and time-dependent changes of ACS patients without RFs. MethodsEvaluation of clinical characteristics, management strategies, and outcomes as well as time-dependent changes [by 3 time periods: early (2000-2006), mid (2008-2013), and late (2016-2018)] of ACS patients without RFs (diabetes mellitus, hypertension, dyslipidemia, family history of ischemic heart disease, and smoking) or known coronary artery disease, enrolled in the biennial ACS Israeli Surveys (ACSIS) between 2000 and 2018. We compared ACS patients without RFs (no-RF group) to those with ≥1 RFs (RF group). ResultsOverall, 554/9,683 (5.7%) eligible ACS patients did not have any RFs [median age 63 (IQR 52-76) years, 25% females]. The no-RF group were older, with lower body mass index and prevalence of other cardiovascular comorbidity and chronic kidney disease compared with the RF group. The in-hospital percutaneous coronary intervention rates were lower among the no-RF vs. the RF group (55% vs. 66%, respectively p<0.001). Furthermore, lower rate of guideline-recommended medical therapy upon discharge was prescribed in the no-RF group. The rate of in-hospital complications was greater in the no-RF vs. RF group (31.6% vs. 26.1%, respectively p=0.005). The rates of 30-day major adverse cardiovascular events (MACE; 17.6% vs.12.8%, respectively, p=0.002) and of 30-day and 1-year all-cause mortality (8.4% vs. 4.2%, p<0.001 and 11.4% vs. 7.7%, p=0.003 respectively) were higher among patients with no-RF vs. RF. Following propensity score matching 30-day MACE, 30-day and 1-year mortality risk remained higher in the no-RF group. The rate of 30-day MACE decreased between the early and the late study period in the no-RF group (21.5% vs. 10.5%, p=0.003, respectively). ConclusionsACS patients without traditional cardiovascular risk-factors comprise a unique group with reduced prevalence of comorbidities yet significantly worse outcomes. Additional research to identify unique risk-factors and targets for interventions to improve outcomes of this group of patients is warranted.

Worse outcomes of ACS patients without versus with traditional cardiovascular risk factors

Abstract Introduction Approximately 5–15% patients presenting with acute coronary syndrome were found to have no traditional cardiovascular risk factors (RFs). Data regarding the determinants, management and outcomes of these patients are scarce. Purpose To evaluate the management, outcomes and time dependent changes of ACS patients without RFs. Methods Evaluation of clinical characteristics, management strategies, and outcomes as well as time dependent changes (by 3 time periods: early [2000–2006], mid [2008–2013], and late [2016–2018]) of ACS patients without RFs (diabetes mellitus, hypertension, dyslipidemia, family history of IHD and current or past smoking) or known coronary artery disease, enrolled in the biennial ACS Israeli Surveys (ACSIS) between 2000 and 2018. We compared ACS patients without RFs (RF−) to those ≥1 RFs (RF+). Results Overall 583 out of 10,324 (5.6%) eligible ACS patients did not have any RFs (median age 64 [IQR 52–77], 25% females]. The RF− group were older, more educated, with lower BMI and prevalence of another cardiovascular comorbidity and chronic kidney disease compared with the RF+ group. The in-hospital PCI rates were lower among the RF− vs. the RF+ group (55% vs. 66%, respectively p&amp;lt;0.001). Furthermore, lower rate of guideline-recommended medical therapy upon discharge were prescribed in the RF− vs. the RF+ group. The rate of in-hospital complications was greater in the RF− vs. RF+ group (31.4% vs. 26.1%, respectively p=0.006). The rates of 30-day major adverse cardiac events (MACE) were significantly higher among patients with RF− vs. RF+ (18.1% vs.12.8%, respectively p&amp;lt;0.001). Similarly, the rates of 30-day and 1-year all-cause mortality (figure 1) were higher among patients with RF− vs. RF+ (8.7% vs. 4.2%, p&amp;lt;0.001 and 11.9% vs. 7.7% p&amp;lt;0.001 respectively). A trend of decline in the rate of MACE was observed between the early and the late study period in the RF− group (22% vs. 10.7% p=0.002 respectively). One-year mortality did not decrease significantly in the RF− group during the study periods (13.6% vs. 10% early vs. late period respectively p=0.16). Conclusions ACS patients without traditional cardiovascular risk factors comprise a unique group with reduced prevalence of comorbidities yet significantly worse short-and long-term outcomes. Additional research to identify unique risk factors and targets for interventions to improve outcomes of this group of patients is warranted. Funding Acknowledgement Type of funding sources: None.

The Affordability of Guideline-Directed Medical Therapy: Cost Sharing is a Critical Barrier to Therapy Adoption.

The Affordability of Guideline-Directed Medical Therapy: Cost Sharing is a Critical Barrier to Therapy Adoption.

An invasive strategy is associated with improved short- and long-term outcomes in acute myocardial infarction independently of frailty status and GRACE score: a nationwide analysis of 12144 episodes

Abstract Introduction Frailty is common among patients presenting with acute myocardial infarction (MI), who have conflicting risks regarding benefits and harms of invasive procedures. Purpose To assess the clinical management and prognostic impact of invasive procedures in frail MI patients in a real-world scenario. Methods We analysed 5422 episodes of ST-elevation MI (STEMI) and 6692 of Non-ST-elevation MI (NSTEMI) recorded from 2010–2019 in a nationwide registry. A validated deficit-accumulation model was used to create a frailty index (FI), comprising 22 features [BMI &amp;gt;25kg/m2, myocardial infarction, angina, heart failure, percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG), valvular disease, bleeding, pacemaker/implantable cardioverter defibrillator, chronic kidney disease (creatinine &amp;gt;2.0mg/dL), dialysis/renal transplant, stroke/transient ischaemic attack, diabetes, hypertension, dyslipidaemia, smoking, peripheral vascular disease, dementia, chronic lung disease, malignancy, polymedication (&amp;gt;3 cardiovascular drugs), admission haemoglobin &amp;lt;10g/dL; not including age]. Episodes with missing data on any FI parameter were not included. Frailty was initially defined as FI&amp;gt;0.25 (i.e. ≥6 features). Results Overall, 511 (9.4%) STEMI and 1763 (26.4%) NSTEMI patients were considered frail. Angiography, PCI and CABG were less frequently performed in frail patients (p&amp;lt;0.001). Delayed angiography (&amp;gt;72h) was more common among NSTEMI frail patients (p&amp;lt;0.001), and radial access was less commonly used overall (p&amp;lt;0.001). Guideline-recommended in-hospital medical therapy, including aspirin (NSTEMI), dual-antiplatelet therapy (STEMI/NSTEMI), heparin/heparin-related agents (NSTEMI), beta-blockers (STEMI) and ACEIs/ARBs (STEMI), was less commonly used in frail patients; discharge medical therapy exhibited similar patterns. Frail patients had longer hospital stay and increased in-hospital all-cause and cardiovascular (CV) mortality, as well as 1-year all-cause and CV hospitalization and all-cause mortality (p&amp;lt;0.001). Using receiver-operator-characteristics curve analysis, FI cutoffs of 0.11 (STEMI) and 0.20 (NSTEMI) yielded the best accuracy to predict 1-year all-cause mortality (area under the curve: 0.629 and 0.702 respectively, p&amp;lt;0.001) – these cutoffs were subsequently used to define frailty. Although frailty attenuated in-hospital risk reductions from angiography (STEMI/NSTEMI) and PCI (NSTEMI only) (Wald test p&amp;lt;0.05), their 1-year prognostic benefit remained unaffected (Wald test p&amp;gt;0.05). Angiography and PCI were associated with improved in-hospital and 1-year outcomes, independently of frailty status or GRACE score (p&amp;lt;0.001). Conclusion Frail MI patients are less commonly offered standard therapy; however, angiography and PCI were associated with short- and long-term prognostic benefits regardless of frailty status or GRACE score. Increased adherence to current recommendations might improve post-MI outcomes in frail patients. Invasive strategy and 1-year outcomes Funding Acknowledgement Type of funding source: Other. Main funding source(s): Portuguese Society of Cardiology