BACKGROUND: The Coronary Slow Flow Phenomenon (CSFP) is considered a coronary microvascular disorder and has been defined as a corrected thrombolysis in myocardial infarction frame count (cTFC) ≥25 frames. Recent invasiv...BACKGROUND: The Coronary Slow Flow Phenomenon (CSFP) is considered a coronary microvascular disorder and has been defined as a corrected thrombolysis in myocardial infarction frame count (cTFC) ≥25 frames. Recent invasive physiology studies have reported that cTFC is not a surrogate marker for coronary microvascular dysfunction (CMD), defined by an abnormal Coronary Flow Reserve (CFR), questioning the integrity of CSFP. This study evaluates the Functional Coronary Angiography (FCA) findings of patients with and without CSFP, as well as the relationship between cTFC and invasive coronary functional measures. METHODS: FCA utilizing a pressure-Doppler flow wire during adenosine infusion, and acetylcholine provocation, was undertaken in 103 patients with angina and non-obstructive coronary artery disease (<50% stenosis; ANOCA). RESULTS: The FCA findings revealed CMD (i.e. CFR<2) in 43%, inducible coronary artery spasm (58%) and microvascular spasm (13%) in patients with the CSFP (n = 69), which was similar to those without CSFP (n = 34). However, the CSFP patients had a lower resting coronary blood flow velocity (19 ± 7 vs 23 ± 7cm/s, P = .009) with higher resting microvascular resistance (5.8 ± 1.9 vs 4.4 ± 1.7mmHg/cm/s, P = .006) and higher hyperemic microvascular resistance (2.35 ± 1.09 vs 1.94 ± 0.93, P = .049), despite a similar hyperemic CFR (2.25 ± 0.84 vs 2.26 ± 0.58, P = .971) compared to those without CSFP. Furthermore, the cTFC as a continuous measure, correlated with resting coronary blood flow, resting/hyperemic resistance but not CFR. CONCLUSION: The conventional marker of CMD (i.e. CFR <2) was similar in patients with/without the CSFP. However alternative hemodynamic markers of impaired coronary microvascular function were abnormal in patients with the CSFP, including resting/hyperemic coronary microvascular resistance. Moreover, cTFC is a simple semi-quantitative marker correlated with coronary microvascular resistance and thus has clinical utility in the diagnosis of the CSFP.
BACKGROUND: Outcomes for patients living with heart failure (HF) remain poor with high rates of death and hospitalization due to worsening HF. Noninvasive tools may be useful to identify patients at risk for disease prog...BACKGROUND: Outcomes for patients living with heart failure (HF) remain poor with high rates of death and hospitalization due to worsening HF. Noninvasive tools may be useful to identify patients at risk for disease progression before these outcomes occur. For example, loss of cell mass and compromised cell membrane integrity throughout the body are associated with chronic disease, mortality, frailty, and malnutrition. As the cell membrane loses its integrity, its electrical capacitance decreases, lowering bioelectrical phase angle. Data collected during the SCALE-HF 1 study (NCT04882449) was used to evaluate bioelectrical phase angle as a marker for heart failure (HF) hospitalization risk. Phase angle was measured by the FDA-cleared Bodyport Cardiac Scale. METHODS: SCALE-HF 1 was a multicenter, prospective, observational study, investigating HF event prediction. Baseline phase angle was measured during the first week in the study with the patient standing barefoot on the Cardiac Scale at home for approximately 20 seconds. HF hospitalizations were independently adjudicated. The analysis was based on univariable and multivariable Cox regression models adjusted for age, sex, race, body mass index (BMI), left ventricular ejection fraction (LVEF), inpatient status at enrollment, and selected comorbidities and laboratory tests. RESULTS: 329 participants with HF were enrolled across 8 US sites with 238 patient-years of follow-up. 312 (95%) of the participants had a baseline phase angle, and 57 (18%) of those had a HF hospitalization during the follow-up period. Participants with baseline phase angle in the lowest quartile (suggesting worse cell membrane integrity) were at increased risk for HF hospitalization compared to participants with baseline phase angle in the highest quartile (Hazard ratio: 3.44, 95% CI: 1.55 to 7.63, P = .002). When adjusted for risk factors selected from age, sex, race, BMI, LVEF, laboratory tests and comorbidities in the multivariable model, participants with baseline phase angle in the lowest quartile continued to be at increased risk for HF hospitalization compared to participants with baseline phase angle in the highest quartile (Hazard ratio: 3.51, 95% CI: 1.73 to 7.12, P < .001). CONCLUSIONS: Phase angle was found to be independently associated with HF hospitalization risk. The noninvasive measurement, acquired with a familiar scale form factor, may help guide remote care and triage. TRIAL REGISTRATION: ClinicalTrials.gov NCT04882449. https://clinicaltrials.gov/study/NCT04882449.
Directly contacting eligible participants with an offer to join a randomized clinical trial (RCT) is an efficient recruitment method, but the effect of different outreach strategies on enrollment fraction and completion...Directly contacting eligible participants with an offer to join a randomized clinical trial (RCT) is an efficient recruitment method, but the effect of different outreach strategies on enrollment fraction and completion of the trial protocol is uncertain. In a study within a trial (SWAT) of an RCT testing a physical activity intervention in patients with peripheral artery disease, eligible patients were randomized to receive an email with an invitation to join the study and a link to the trial's online platform ("opt-in") or to receive an email framing participation as part of the standard of care followed by telephone outreach from a study coordinator ("opt-out"). Among 5176 participants contacted by unsolicited email (3909 opt-in, 1267 opt-out), enrollment fraction was 1.0% in the opt-in arm (n = 39) versus 3.6% in the opt-out arm (n = 45) (OR 3.65, 95% CI 2.37-5.64); there were no significant differences between opt-in and opt-out participants in the rate of completion of trial protocol steps. This SWAT of recruitment strategies demonstrates the potential for opt-out framing and active outreach to increase enrollment fraction without compromising protocol completion in direct-to-participant RCTs.
Abdelaziz A, Ramadan S, Hasan MT
… +18 more, Desouky M, Atta K, Hafez A, Shams MM, Helmi A, Ibrahim RA, Sobhy A, Diab RA, Rzk FM, Gadelmawla AF, Alenna ZM, Abdelaziz M, Hamouda MN, Hammad N, Lorenzatti D, Lavie CJ, Slipczuk L, Stone GW
Complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease reduces major adverse cardiac events (MACE) compared with incomplete revascularization, although whet...Complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease reduces major adverse cardiac events (MACE) compared with incomplete revascularization, although whether survival is improved is uncertain. For this systematic review and meta-analysis, all randomized trials of complete vs incomplete revascularization in patients with acute MI without cardiogenic shock were identified from PubMed, Scopus, Web of Science, and Cochrane Library databases from inception to December 31, 2024. The primary and major secondary endpoints were MACE and all-cause mortality derived from reconstructed time-to-event individual-patient-data from published Kaplan-Meier curves. Additional outcomes included cardiovascular mortality, MI, and unplanned repeat revascularizations. Outcomes were expressed as hazard ratios with 95% confidence intervals. This study was registered with the PROSPERO (number, CRD42023415428). A total of 9 randomized trials with 9,658 patients (86.8% with STEMI) were identified among whom 4,671 (48.4%) patients had complete revascularization. Patients with complete revascularization had a lower 5-year risk of MACE (HR: 0.59, 95% CI: 0.54 to 0.66, P < .001) compared with incomplete revascularization. Complete revascularization was also associated with lower 5-year risks of all-cause mortality (HR: 0.64, 95% CI: 0.56 to 0.72, P < .001), cardiovascular mortality (HR: 0.82, 95% CI: 0.71 to 0.95, P = .008), MI (HR: 0.69, 95% CI: 0.55 to 0.87, P < .001), and unplanned repeat revascularizations (HR: 0.62, 95% CI: 0.54 to 0.71, P < .001). Complete revascularization results in lower risks of all-cause and cardiovascular mortality, MI, unplanned repeat revascularizations and MACE in patients with acute MI and multivessel disease. These results support current guidelines recommending CR in hemodynamically stable patients with STEMI, emphasizing that this approach may improve survival.
BACKGROUND: Mavacamten, a first-in-class cardiac myosin inhibitor, is approved internationally for the treatment of symptomatic adult patients with obstructive hypertrophic cardiomyopathy (HCM) and has been shown to impr...BACKGROUND: Mavacamten, a first-in-class cardiac myosin inhibitor, is approved internationally for the treatment of symptomatic adult patients with obstructive hypertrophic cardiomyopathy (HCM) and has been shown to improve cardiac function and symptoms in adult patients across multiple phase 3 trials. The efficacy and safety of mavacamten in pediatric patients with obstructive HCM has not been evaluated. METHODS: SCOUT-HCM is a phase 3, randomized, placebo-controlled, double-blind, parallel-group, multicenter, international study in symptomatic adolescent patients (12 years to <18 years old) with obstructive HCM. The aim of the study is to assess the efficacy, safety, and pharmacokinetics of mavacamten in this population. Participants will be randomized 1:1 to mavacamten or placebo for 28 weeks, followed by a 28-week active-treatment period (when patients randomized to placebo will cross over to mavacamten) and an open-label long-term extension period for ≤144 weeks. Participants will initiate mavacamten at a dosage of 2.5 mg/day or 5 mg/day; dose titration will be based on echocardiographic assessment of Valsalva left ventricular (LV) outflow tract (LVOT) gradient and LV ejection fraction. The primary endpoint is change from baseline to week 28 in Valsalva LVOT gradient. Secondary endpoints include efficacy parameters of resting and post-exercise LVOT gradients, peak oxygen consumption, symptoms, and health status, plus safety and pharmacokinetic parameters. CONCLUSIONS: SCOUT-HCM is the first clinical trial to evaluate a cardiac myosin inhibitor in adolescent patients with obstructive HCM. SCOUT-HCM will assess the utility of mavacamten in this patient population with an unmet clinical need. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06253221.
Hill KD, Koerner J, Hong H
… +23 more, Li JS, Hornik C, Kannankeril PJ, Jacobs JP, Baldwin HS, Jacobs ML, Graham EM, Blasiole B, Vener DF, Husain AS, Kumar SR, Benscoter A, Wald E, Karamlou T, Van Bergen AH, Overman D, Eghtesady P, Butts R, Kim JS, Scott JP, Anderson BR, Swartz MF, O'Brien SM
BACKGROUND: Prophylactic steroids are often used to reduce the systemic inflammatory response to cardiopulmonary bypass in infants undergoing heart surgery. The STRESS trial found that the odds of a worse outcome did not...BACKGROUND: Prophylactic steroids are often used to reduce the systemic inflammatory response to cardiopulmonary bypass in infants undergoing heart surgery. The STRESS trial found that the odds of a worse outcome did not differ between infants randomized to methylprednisolone (n = 599) versus placebo (n = 601) (adjusted odds ratio [OR], 0.86; P = .14). However, secondary analyses showed possible benefits with methylprednisolone. To investigate further using a different probabilistic approach, we re-analyzed the STRESS trial using Bayesian analytics. METHODS: We used a covariate-adjusted proportional odds model using the original STRESS trial primary endpoint, a ranked composite of death, transplant, major complication and post op length of stay. We performed Markov Chain Monte Carlo simulations to assess the probability of benefit (OR < 1) versus harm (OR > 1). Primary analysis assumed a neutral probability of benefit versus harm with weak prior belief strength (nearly noninformative prior distribution). To illustrate magnitude of effect, we calculated predicted risk of death, transplant or major complications for methylprednisolone and placebo. Sensitivity analyses evaluated pessimistic (5%-30% prior likelihood of benefit), neutral and optimistic (70%-95%) prior beliefs, and controlled strength of prior belief as weak (30% variance), moderate (15%) and strong (5%). A secondary analysis derived empirical priors using data from four previous steroid trials. RESULTS: The posterior probability of any benefit from methylprednisolone was 92% and probability of harm was 8%. Composite death or major complication occurred in 18.8% of subjects with an absolute risk difference of -2% (95% CI -3%, +1%) for methylprednisolone. Each of 9 sensitivity analyses demonstrated greater probability of benefit than harm in the methylprednisolone group with 8 of 9 demonstrating >80% probability of benefit and ≥1% absolute difference in risk of death, transplant or major complications. In secondary analysis deriving priors from previous steroid trials, results were consistent with a 95% posterior probability of benefit. CONCLUSION: Our Bayesian re-analysis of the STRESS trial, using a range of prior beliefs, demonstrated a high probability that perioperative methylprednisolone reduces the risk of death or major complications in infants undergoing cardiopulmonary bypass compared with placebo. This more in-depth analysis expands the initial clinical evaluation of methylprednisolone provided by the STRESS trial. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03229538 (https://clinicaltrials.gov/study/NCT03229538).
BACKGROUND: Real-world characteristics and outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF) treated with vericiguat remain unclear. We investigated patient characteristics, hypotension-t...BACKGROUND: Real-world characteristics and outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF) treated with vericiguat remain unclear. We investigated patient characteristics, hypotension-the most relevant clinical event-, and outcomes after initiating vericiguat in patients with HFrEF. METHODS: In this nationwide, multicentre retrospective study involving 22 hospitals in Japan, we examined symptomatic or asymptomatic hypotension and drug discontinuation within 90 days after initiation of vericiguat in patients with left ventricular ejection fraction <45%. The association between hypotension and HF outcomes was also examined. RESULTS: Among the 799 patients with HFrEF, the mean age was 69.6 years, and 218 (27.3%) were female. Of them, 316 (39.5%) had New York Heart Association classification III or IV, and 329 (41.8%) had systolic blood pressure (sBP) <100 mm Hg. Hypotension was observed in 25.3% of patients within 90 days, with asymptomatic hypotension being the most common (17.9%). By contrast, drug discontinuation related to hypotension was less frequent (4.4%). After adjustment, sBP <100 mm Hg, low body mass index, and in-hospital vericiguat initiation were associated with the incidence of hypotension within 90 days. Patients who experienced hypotension had a greater risk of cardiovascular death or HF hospitalization than those who did not (P = .01). CONCLUSIONS: Although hypotension was relatively common soon after starting vericiguat, they were not often associated with drug discontinuation. Patients experiencing hypotension had a greater risk of HF outcomes, but this would be primarily associated with their vulnerability, given the infrequent discontinuation.
BACKGROUND: Lifestyle modification is a key pillar of atrial fibrillation (AF) management. Yoga has beneficial effects on cardiovascular health and has shown promise as an intervention in AF. However, randomized data are...BACKGROUND: Lifestyle modification is a key pillar of atrial fibrillation (AF) management. Yoga has beneficial effects on cardiovascular health and has shown promise as an intervention in AF. However, randomized data are absent. OBJECTIVES: To determine the effect of regular yoga on AF episodes and AF burden in people with paroxysmal or persistent AF over a 12-month period. METHODS: This is a randomized control trial of a yoga program in addition to standard care, compared to standard care alone in people with paroxysmal or persistent AF undergoing a rhythm control management strategy. 222 participants will be randomized 1:1 to the yoga intervention or control. Yoga will be conducted in studio and online with a target of at least 3 classes/week. Controls will be instructed to exercise for at least 150 minutes/week. Rhythm monitoring will be with implantable loop recorder, or ECG capable smartwatch with AF detection and twice daily ECGs. Autonomic metrics will be assessed in the laboratory by HRV, blood pressure variability and direct recordings of muscle sympathetic nerve activity. Following a 3-month training period, the dual primary endpoints of AF recurrence (time to recurrence, as defined by any sustained atrial tachyarrhythmia lasting >1 hour) and AF burden will be determined at 12 months. CONCLUSIONS: This study aims to determine the impact of yoga on AF recurrence and burden in people with paroxysmal and persistent AF. Yoga may provide an effective noninvasive, nonpharmacologic lifestyle strategy in the management of AF. TRIAL REGISTRATION: The trial was preregistered with the Australian New Zealand Clinical Trials Registry (ACTRN12624000264583).
BACKGROUND: Clinical guidelines advocate use of validated risk models in patients experiencing heart failure with reduced ejection fraction (HFrEF) to inform prognosis and assist with management. We developed models for...BACKGROUND: Clinical guidelines advocate use of validated risk models in patients experiencing heart failure with reduced ejection fraction (HFrEF) to inform prognosis and assist with management. We developed models for worsening HF (WHF) hospitalizations and death within 1 year of incident HFrEF using data available within electronic health records (EHR). METHODS: Adults with incident HFrEF were identified from 2013 to 2022 within an integrated healthcare delivery system. We developed decision tree-based models to estimate risks of WHF hospitalization and death within 1 year of the incident HFrEF date. WHF hospitalizations were ascertained using validated natural language processing algorithms. We evaluated the models using cross-validation and measured final performance (i.e., model discrimination using area under the curve [AUC] and model calibration using the Brier score and calibration plots) on a contemporary hold-out test set of patients from 2021 to 2022. RESULTS: Among 28,292 adults with incident HFrEF, 17.3% experienced WHF hospitalization and 15.1% all-cause death at 1 year of follow-up. We observed an AUC of 0.698 (95% CI: 0.682-0.714) for WHF hospitalization and 0.849 (95% CI: 0.836-0.861) for death and calibrated with a wide range of predicted risks. In comparison, a claims-based risk score displayed an AUC of 0.577 (95% CI: 0.570-0.606) for WHF hospitalization and a smaller dynamic range. Of patients classified as high risk for WHF hospitalization, only 12.0% were receiving full guideline-directed medical therapy at 6 months after HFrEF diagnosis. CONCLUSION: Risk models derived using EHR-based data elements can predict both 1-year WHF hospitalization and all-cause mortality in adults with incident HFrEF more accurately than claims-based approaches. These models can be used to improve population management and better target personalized strategies of care.
BACKGROUND: Excessive aortic cusp calcification increases the risk of periprocedural complications after transcatheter aortic valve replacement (TAVR). Differences in device performance in patients with excessive calcifi...BACKGROUND: Excessive aortic cusp calcification increases the risk of periprocedural complications after transcatheter aortic valve replacement (TAVR). Differences in device performance in patients with excessive calcification may affect long-term clinical outcomes. OBJECTIVES: To compare periprocedural and long-term outcomes between self-expanding (SEV) and balloon-expandable (BEV) prostheses in patients with excess cusp calcification undergoing TAVR. METHODS: Consecutive patients with severe aortic stenosis and aortic valve complex calcium volume ≥235 mm³ (on contrast images with Hounsfield unit threshold of 850) who underwent TAVR with either CoreValve/Evolut SEV or SAPIEN BEV from August 2007 to June 2023 were included from a prospective-single center registry. A 1:1 propensity-matched analysis was performed to account for baseline differences between groups. RESULTS: Among 1,345 patients with excessive cusp calcification undergoing TAVR, 271 matched pairs were identified. Procedural success was achieved in >85% of patients with no difference between groups. Annular rupture occurred more frequently with BEV compared to SEV (2.2% vs 0%, P = .030). SEV had a lower transprosthetic gradient (8.0 mmHg vs 11.2 mmHg, P < .001) but higher rates of mild or greater paravalvular regurgitation (69.7% vs 58.1%, P = .008) and new permanent pacemaker implantation (22.6% vs 15.5%, P = .001). At 5 years, there was no statistically significant difference in mortality between groups (45.1% vs 50.2%, P = .173). CONCLUSIONS: In patients with excessive leaflet calcification undergoing TAVR, BEV had a higher risk of annular rupture, but a lower risk of paravalvular regurgitation, and a lower risk of permanent pacemaker implantation compared to SEV. Mortality was comparable between SEV and BEV throughout 5 years of follow-up. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. NCT01368250.
We investigated whether cumulative fasting glucose (FG) and insulin resistance (IR) over 20 years are associated with midlife cardiac dysfunction in young adults with or without type 2 diabetes (T2D)/prediabetes. We incl...We investigated whether cumulative fasting glucose (FG) and insulin resistance (IR) over 20 years are associated with midlife cardiac dysfunction in young adults with or without type 2 diabetes (T2D)/prediabetes. We included young adults with T2D/prediabetes (N = 279) and matched euglycemic individuals (N = 514) who had repeated measures of fasting glucose (FG) and insulin resistance (IR) and echocardiography assessment from the Coronary Artery Risk Development in Young Adults study (CARDIA). We found that cumulative hyperglycemia is associated with midlife diastolic dysfunction in patients with early-onset T2D, and sustained IR negatively affects systolic and diastolic function regardless of T2D status.
BACKGROUND: Adult cancer survivors are at increased risk of heart failure (HF) due to standard risk factors and cancer treatment-related cardiac dysfunction. However, the prevalence and treatment of subclinical/stage B h...BACKGROUND: Adult cancer survivors are at increased risk of heart failure (HF) due to standard risk factors and cancer treatment-related cardiac dysfunction. However, the prevalence and treatment of subclinical/stage B heart failure (SBHF) in this population are not well defined. OBJECTIVES: The REDEEM (Risk-guided Disease managEment plan to prevEnt heart failure in patients treated with previous cardiotoxic cancer treatMents) trial will evaluate HF screening and targeted intervention in long-term cancer survivors. METHODS: Survivors ≥40 years old, ≥5 years post potentially-cardiotoxic therapy, and with ≥1 HF risk factor were screened by echocardiography for SBHF (abnormal global longitudinal shortening [GLS], left ventricular hypertrophy [LVH], diastolic dysfunction or abnormal 3-dimensional left ventricular ejection fraction [3D-LVEF]). Those with SBHF were randomized to multidisciplinary cardio-oncology disease management plan (CO-DMP), including neurohormonal blockade, exercise training and risk factor optimization, or usual care. The primary endpoint is change in cardiorespiratory fitness (VOpeak) over 6 months. RESULTS: Of 1,124 survivors screened, 604 underwent echocardiography, and 145 (24%) had SBHF (age 68±18 years; 81% women). Of those eligible for randomization, 64% had breast cancer and 35% had hematological malignancy. Although baseline 3D-LVEF was preserved (52.8 ± 6.8%), subclinical LV dysfunction was common (GLS 15.6 ± 2.1%) and 39% had evidence of functional impairment (VOpeak≤18ml/kg/min). Abnormal GLS was associated with age, BMI, diabetes and anthracycline exposure, whereas functional impairment was only associated with age. Abnormal GLS and functional impairment were not significantly associated (OR 0.90 [95% CI 0.72-1.11], P = .360). CONCLUSIONS: Risk-based screening can identify a high-risk subpopulation of cancer survivors with SBHF. REGISTRATION: ClinicalTrials.gov NCT04962711, https://www. CLINICALTRIALS: gov/study/NCT04962711.
BACKGROUND: Percutaneous catheter-based left atrial appendage (LAA) closure is a potential alternative to oral anticoagulation for stroke prevention in patients with atrial fibrillation (AF). The effectiveness and safety...BACKGROUND: Percutaneous catheter-based left atrial appendage (LAA) closure is a potential alternative to oral anticoagulation for stroke prevention in patients with atrial fibrillation (AF). The effectiveness and safety of LAA closure in patients with AF at high risk of stroke (CHA2DS2-VASc Score ≥2) and high risk of bleeding compared to best medical care including a nonvitamin K antagonist oral anticoagulant [NOAC] when considered eligible is not known. METHODS/DESIGN: The prospective, multicenter, randomized clinical Left atrial appendage CLOSURE in patients with Atrial Fibrillation at high risk of stroke and bleeding compared to medical therapy (CLOSURE-AF) trial compared catheter-based LAA closure to best medical care (including NOAC therapy if considered eligible) in patients with AF at high risk of stroke and with either a history of bleeding or a high estimated bleeding risk (HASBLED ≥ 3). The primary endpoint is time to a composite of first stroke (ischemic or hemorrhagic), systemic embolism, cardiovascular or unexplained death or major bleeding (Bleeding Academic Research Consortium 3-5). Secondary outcomes include components of the primary outcome and total mortality. The primary efficacy analysis will be performed in the intention-to-treat population using Cox regression models for noninferiority with an option to test for superiority once noninferiority has been proven. RESULTS: The first patient in the CLOSURE-AF trial was enrolled in March 2018. By April 2025 the complete study cohort of n = 912 patients had been enrolled in 42 sites. CONCLUSION: CLOSURE-AF will contribute evidence on the effectiveness and safety of LAA occlusion compared to optimal medical therapy in patients with AF at high risk of stroke and bleeding. The trial results will help to define the clinical use of catheter-based LAA closure in the future. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03463317.
Lerman JB, Koeberl DD, Epstein S
… +12 more, Roessig L, Stan R, Halley M, Owens AT, Greenberg B, Alexander KM, Day SM, Maurer MS, Adler ED, Hernandez AF, Ashley EA, Felker GM
Rare cardiovascular diseases, while individually uncommon, collectively affect millions of people worldwide and are associated with significant morbidity, mortality, and economic burden. Despite this considerable impact,...Rare cardiovascular diseases, while individually uncommon, collectively affect millions of people worldwide and are associated with significant morbidity, mortality, and economic burden. Despite this considerable impact, most rare cardiovascular diseases lack approved treatments. Developing therapies for rare cardiovascular diseases requires overcoming a unique set of challenges. This includes barriers to accurate patient diagnosis (and therefore to trial cohort generation), small cohort sizes, the choice of effective clinical trial endpoints, unique ethical and regulatory concerns, and the often-substantial costs of such therapies (which may limit public access to treatment). Despite such challenges, the past decade has witnessed a significant increase in the successful development of rare cardiovascular disease therapies. This review provides an overview of the challenges, while also highlighting potential strategies to advance the field.
BACKGROUND: Current guidelines recommend a combination therapy with aspirin and a parenteral anticoagulant in patients with non-ST-elevation myocardial infarction (NSTEMI) prior to invasive assessment. However, these rec...BACKGROUND: Current guidelines recommend a combination therapy with aspirin and a parenteral anticoagulant in patients with non-ST-elevation myocardial infarction (NSTEMI) prior to invasive assessment. However, these recommendations are based on clinical trials conducted at a time when NSTEMI patients were not routinely assessed invasively. Today, nearly all NSTEMI patients in Denmark undergo coronary angiography within 72 hours, and the necessity of routine anticoagulation remains uncertain. The FOXY trial aims to assess whether aspirin alone is noninferior to a combination therapy with aspirin and fondaparinux in preventing death, recurrent myocardial infarction, and refractory ischemia while lowering the risk of bleeding. TRIAL DESIGN: The FOXY trial is a multicenter, open-label, noninferiority, randomized controlled trial enrolling 5,076 patients with NSTEMI. Participants will be randomized 1:1 to receive either aspirin alone or aspirin plus fondaparinux before invasive evaluation. The primary endpoint is a composite of 30-day mortality, recurrent MI, and refractory ischemia. Secondary outcomes include long-term ischemic events, cerebrovascular accidents, left ventricular function, hospital length of stay, and major bleeding. The study will be conducted across multiple cardiology centers, with the first patients enrolled in spring 2025. CONCLUSION AND PERSPECTIVE: The FOXY trial is the first study to investigate parenteral anticoagulant use in NSTEMI patients undergoing routine invasive management. By comparing aspirin alone to combination therapy, the study seeks to challenge current guideline recommendations and potentially simplify NSTEMI treatment. If noninferiority is demonstrated, the trial may support a shift toward a safer and more cost-effective management of NSTEMI patients. This could lead to a revision of clinical guidelines, minimizing bleeding risk, improving patient safety, and reducing healthcare costs. TRIAL REGISTRATION: EU Trial Number: 2024-517229-18-00; ClinicalTrials.gov identifier: NCT06710184.
BACKGROUND: Athlete's heart, characterized by cardiac chambers adaptations to exercise has some diagnostic overlaps with dilated cardiomyopathy (DCM). In the setting of differential diagnosis, myocardial work indexes (MW...BACKGROUND: Athlete's heart, characterized by cardiac chambers adaptations to exercise has some diagnostic overlaps with dilated cardiomyopathy (DCM). In the setting of differential diagnosis, myocardial work indexes (MWI), afterload-independent tool, could be helpful to identify early subclinical alterations. The aim of our study was to assess the utility of MWI in athletes with mildly reduced left ventricular ejection fraction (LVEF). METHODS: We enrolled 306 Olympic athletes (55.5% males) practicing endurance and mixed disciplines, mean age 26.3 ± 4.3 years old, who underwent cardio-pulmonary exercise test (CPET) and transthoracic echocardiogram. Athletes were divided in those with lower (<55%) and normal LVEF (≥55%). Strain rate and MWI were performed and the following parameters collected: global longitudinal strain, global myocardial work index (GWI), constructive myocardial work (CMW), wasted myocardial work (WMW) and global cardiac work efficiency (GWE). RESULTS: Twenty-seven athletes had LVEF<55% (mean 51.5% ± 2.6%). Athletes with EF < 55% presented larger LVEDVi (79.1 ± 15.7 vs. 73.2 ± 13.8 mm/m2, P = .035), LV mass (P = .049) and LAVi (P = .016). No differences were found in GWI (1,757.9 ± 242 vs 1,839.8 ± 255.6 mmHg%, P = .112), GCW (2,121.6 ± 269.3 vs. 2,209.3 ± 281 mmHg%, P = .124), GWW (95.2 ± 40.7 vs. 87.1 ± 47.4 mmHg%, P = .394) or GWE (95.2 ± 1.7 vs. 95.7 ± 2%, P = .181). At CPET, in those with EF < 55%, higher Watts (340.0 ± 83.7 vs. 291.6 ± 84.8, P = .004), VO mL/min/Kg (51.0 ± 13.5 vs. 46.0 ± 10.1, P = .020) and O2 pulse (23.5 ± 4.6 vs. 21 ± 5.3, P = .020) were found. CONCLUSIONS: MWI could be used as additive tool to characterize the physiologic nature of mildly reduced EF of endurance athletes, presenting with better functional parameters but preserved MWI values. MWI may be helpful in differential diagnosis of athlete's heart from DCM.
Goldenberg I, Zareba W, Ezekowitz JA
… +25 more, Albert C, Alexis JD, Anderson L, Behr ER, Daubert J, Di Palo KE, Ellenbogen KA, Dzikowicz DJ, Harrington JM, Hsich E, Huang DT, Januzzi JL, Jawaid A, Kutyifa V, Lala-Trindade A, Nakonechnyi A, Onwuanyi A, Piña IL, Sandhu RK, Sears S, Sroubek J, Baykaner T, Strawderman R, Beck C, Butler J
BACKGROUND: Current recommendations for a prophylactic (primary prevention) implantable cardioverter defibrillator (ICD) in patients with both ischemic and nonischemic heart failure with reduced ejection fraction (HFrEF)...BACKGROUND: Current recommendations for a prophylactic (primary prevention) implantable cardioverter defibrillator (ICD) in patients with both ischemic and nonischemic heart failure with reduced ejection fraction (HFrEF) originate from clinical trials conducted in selected patients over 20 years ago that showed an overall statistically significant survival benefit associated with a primary prevention ICD in the range of 23%-34%. The recent introduction of angiotensin receptor-neprilysin inhibitors [ARNI] and sodium glucose co-transporter 2 inhibitors [SGLT2i]) was shown to further reduce the risk of sudden cardiac death (SCD) in patients with HFrEF. Thus, there is an unmet need appropriately designed comparative effectiveness clinical trials aimed to reassess the survival benefit of a primary prevention ICD in contemporary patients with HFrEF. METHODS: The comparative effectiveness of ICD vs non-ICD therapy in contemporary heart failure patients at a low risk for arrhythmic death (CONTEMP-ICD) trial is a prospective, multicenter, open-label, randomized-controlled trial; enrolling 3,290 participants with HFrEF who are treated with optimal stable GDMT and are eligible for a primary prevention ICD, but have a lower predicted risk of life-threatening ventricular tachyarrhythmia (VTA) than nonarrhythmic mortality. Enrolled participants will be randomized to non-ICD vs ICD treatment arms and will be followed over an average period of 3.5 years. The specific aims of the proposed clinical trial are to: (1) Compare the risk of all-cause mortality of non-ICD vs ICD in HFrEF patients who have a lower predicted risk of VTA than nonarrhythmic mortality per the MADIT-ICD Benefit Score; (2) Evaluate whether non-ICD vs ICD is associated with improved survival free of major CV events in patients with HFrEF who are at a lower predicted arrhythmic risk; (3) Assess healthcare utilization and quality of life implications of non-ICD vs ICD management approaches in HFrEF patients who are at a lower predicted arrhythmic risk; and (4) Determine the effect of non-ICD vs ICD management on all-cause mortality in prespecified subgroups. CONCLUSIONS: We hypothesize that, in patients with HFrEF who are at a lower predicted arrhythmic risk, non-ICD vs ICD is noninferior with respect to the primary endpoint of all-cause mortality and superior with respect to the secondary endpoint of survival free of major CV events. NCT06543446; https://contemp-icd.org.
de Rojas JP, Toledo E, Estruch R
… +16 more, Guasch-Ferré M, Salas-Salvadó J, Gómez-Gracia E, Ros E, Fitó M, Arós F, Fiol M, Lapetra J, Serra-Majem L, Pintó X, Sorlí JV, Babio N, Castañer O, Alonso-Gómez ÁM, Martínez-González MÁ, Jiménez-Moleón JJ
BACKGROUND: Olive oil, increasingly consumed in the U.S., has been inversely associated with cardiovascular disease (CVD) risk. However, previous studies did not assess a broad spectrum of CVD outcomes, incorporated repe...BACKGROUND: Olive oil, increasingly consumed in the U.S., has been inversely associated with cardiovascular disease (CVD) risk. However, previous studies did not assess a broad spectrum of CVD outcomes, incorporated repeated annual dietary assessments, or distinguished between polyphenol-rich EVOO and common olive oil (COO), which lacks these compounds. METHODS: We assessed 7102 high-risk participants from the PREDIMED trial (57.5% women; aged 55-80 years), all free of CVD at baseline. Olive oil consumption was assessed annually, and cumulative average intakes of EVOO and COO were calculated. The primary outcome was a composite of myocardial infarction, stroke, peripheral arterial disease, heart failure, atrial fibrillation, or cardiovascular death, whichever occurred first. Individual outcomes were also evaluated. Time-dependent Cox models were adjusted for major confounders, including trial intervention arm. RESULTS: Over a median follow-up of 4.7 years, 621 participants experienced at least one CVD event. Participants in the highest tertile of cumulative EVOO intake (mean: 49.2 g/d) had a 25% lower risk of the composite outcome (HR: 0.75; 95% CI: 0.60-0.94), with significant reductions in several individual CVD outcomes. In the decile analysis, the highest (mean: 60.9 g/d) versus lowest decile had a 48% lower risk (HR: 0.52; 95% CI: 0.35 to 0.79). COO consumption was not significantly associated with CVD risk when mutually adjusted for EVOO (HR: 0.93; 95% CI: 0.87-1.00). CONCLUSIONS: High consumption of EVOO is associated with a substantial reduction in the risk of an outcome-wide composite of CVD events among high-risk individuals. In contrast, COO, which lacks polyphenols, showed weaker associations, highlighting the importance of differentiating olive oil types in CVD prevention strategies. TRIAL REGISTRATION: This trial was registered in the ISRCTN registry (ISRCTN 35739639): https://www.isrctn.com/ISRCTN35739639.