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Representativeness in randomized clinical trials remains a critical concern, affecting the external validity of trial results, equitable access to the risks and benefits of research participation, and public trust in clinical research. Although representative participation by members of groups traditionally underrepresented in clinical trials is just a surrogate for true diversity, equity, inclusion, and belonging in clinical trials, it can be quantified, allowing stakeholders to add empirical rigor to diversity, equity, inclusion, and belonging efforts. Multiple ways to measure representativeness have been proposed, including the participation-to-prevalence ratio, raw participation proportions or numbers for relevant subgroups, and enrollment fraction for relevant subgroups. These methods have strengths and weaknesses and may be appropriate to report in certain circumstances, depending on why stakeholders seek to assess representativeness. Stakeholders—including regulatory agencies, journal editors, clinical trial investigators, and trial sponsors—may use quantitative measures of representativeness to establish trial enrollment standards, monitor equitable participation in ongoing trials, and condition funding or drug or device approval on achieving specific representativeness targets. However, using quantitative measures of representativeness in this way could have unintended consequences, including researchers "gaming" recruitment strategies to meet target numbers, overlooking nuanced variations within communities, and potentially incentivizing problematic and exploitative recruitment strategies. Although no single method of measuring representativeness offers a comprehensive solution for increasing diversity, equity, inclusion, and belonging in all randomized clinical trials, a carefully designed, multifaceted approach to measuring representativeness may provide stakeholders with useful perspectives for measuring progress in increasing the diversity of clinical trial participation. For stakeholders seeking a single number to assess the representativeness of a trial enrolling patients with a disease state with well-delineated demographics, the participation-to-prevalence ratio is ideal; however, for a more nuanced view of representativeness, the combination of enrollment fraction in subgroups of relevance plus a full report of the demographics of patients approached for enrollment may be more appropriate. [ABSTRACT FROM AUTHOR]

The article "Cardiac Resynchronization Therapy: New Perspectives" discusses the benefits of cardiac resynchronization therapy (CRT) in heart failure patients, highlighting its ability to reduce morbidity and mortality, reverse left ventricular remodeling, and improve quality of life. The article also addresses disparities in CRT use, gaps in existing evidence, and emerging pacing technologies such as His bundle pacing and left bundle branch area pacing. The authors emphasize the importance of identifying suitable patients for CRT and the need for simplified guidelines to improve implementation. [Extracted from the article]

The editorial discusses the role of percutaneous coronary intervention (PCI) in relieving angina in patients with chronic coronary syndrome. Studies like FAME 2 and ISCHEMIA have shown that PCI improves angina and quality of life compared to medical therapy alone, although survival rates were similar. The article also highlights the importance of coronary physiology in predicting angina relief after PCI, emphasizing the need for a more comprehensive assessment to optimize patient selection for the procedure. The Xiangya School of Medicine at Central South University, with its renowned Cardiology Departments in affiliated hospitals, is nationally recognized for excellence in cardiovascular care. [Extracted from the article]

Balloon pulmonary angioplasty continues to gain traction as a treatment option for patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. Recent European Society of Cardiology guidelines on pulmonary hypertension now give balloon pulmonary angioplasty a Class 1 recommendation for inoperable and residual chronic thromboembolic pulmonary hypertension. Not surprisingly, chronic thromboembolic pulmonary hypertension centers are rapidly initiating balloon pulmonary angioplasty programs. However, we need a comprehensive, expert consensus document outlining critical concepts, including identifying necessary personnel and expertise, criteria for patient selection, and a standardized approach to preprocedural planning and establishing criteria for evaluating procedural efficacy and safety. Given this lack of standards, the balloon pulmonary angioplasty skill set is learned through peer-to-peer contact and training. This document is a state-of-the-art, comprehensive statement from key thought leaders to address this gap in the current clinical practice of balloon pulmonary angioplasty. We summarize the current status of the procedure and provide a consensus opinion on the role of balloon pulmonary angioplasty in the overall care of patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. We also identify knowledge gaps, provide guidance for new centers interested in initiating balloon pulmonary angioplasty programs, and highlight future directions and research needs for this emerging therapy. [ABSTRACT FROM AUTHOR]

Although heart transplantation is the preferred therapy for appropriate patients with advanced heart failure, the presence of concomitant renal or hepatic dysfunction can pose a barrier to isolated heart transplantation. Because donor organ supply limits the availability of organ transplantation, appropriate allocation of this scarce resource is essential; thus, clear guidance for simultaneous heart-kidney transplantation and simultaneous heart-liver transplantation is urgently required. The purposes of this scientific statement are (1) to describe the impact of pretransplantation renal and hepatic dysfunction on posttransplantation outcomes; (2) to discuss the assessment of pretransplantation renal and hepatic dysfunction; (3) to provide an approach to patient selection for simultaneous heart-kidney transplantation and simultaneous heart-liver transplantation and posttransplantation management; and (4) to explore the ethics of multiorgan transplantation. [ABSTRACT FROM AUTHOR]

Menopausal hormone therapy (HT) was widely used in the past, but with the publication of seminal primary and secondary prevention trials that reported an excess cardiovascular risk with combined estrogen-progestin, HT use declined significantly. However, over the past 20 years, much has been learned about the relationship between the timing of HT use with respect to age and time since menopause, HT route of administration, and cardiovascular disease risk. Four leading medical societies recommend HT for the treatment of menopausal women with bothersome menopausal symptoms. In this context, this review, led by the American College of Cardiology Cardiolovascular Disease in Women Committee, along with leading gynecologists, women’s health internists, and endocrinologists, aims to provide guidance on HT use, including the selection of patients and HT formulation with a focus on caring for symptomatic women with cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

Background: Extensive evidence from single-center studies indicates that a subset of patients with chronic advanced heart failure (HF) undergoing left ventricular assist device (LVAD) support show significantly improved heart function and reverse structural remodeling (ie, termed "responders"). Furthermore, we recently published a multicenter prospective study, RESTAGE-HF (Remission from Stage D Heart Failure), demonstrating that LVAD support combined with standard HF medications induced remarkable cardiac structural and functional improvement, leading to high rates of LVAD weaning and excellent long-term outcomes. This intriguing phenomenon provides great translational and clinical promise, although the underlying molecular mechanisms driving this recovery are largely unknown.Methods: To identify changes in signaling pathways operative in the normal and failing human heart and to molecularly characterize patients who respond favorably to LVAD unloading, we performed global RNA sequencing and phosphopeptide profiling of left ventricular tissue from 93 patients with HF undergoing LVAD implantation (25 responders and 68 nonresponders) and 12 nonfailing donor hearts. Patients were prospectively monitored through echocardiography to characterize their myocardial structure and function and identify responders and nonresponders.Results: These analyses identified 1341 transcripts and 288 phosphopeptides that are differentially regulated in cardiac tissue from nonfailing control samples and patients with HF. In addition, these unbiased molecular profiles identified a unique signature of 29 transcripts and 93 phosphopeptides in patients with HF that distinguished responders after LVAD unloading. Further analyses of these macromolecules highlighted differential regulation in 2 key pathways: cell cycle regulation and extracellular matrix/focal adhesions.Conclusions: This is the first study to characterize changes in the nonfailing and failing human heart by integrating multiple -omics platforms to identify molecular indices defining patients capable of myocardial recovery. These findings may guide patient selection for advanced HF therapies and identify new HF therapeutic targets. [ABSTRACT FROM AUTHOR]

Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist and share pathophysiological mechanisms. The proportion of patients with AS and CAD requiring revascularization varies widely because of uncertainty about best clinical practices. Although combined surgical aortic valve replacement and coronary artery bypass grafting has been the standard of care, management options in patients with AS and CAD requiring revascularization have expanded with the advent of transcatheter aortic valve replacement (TAVR). Potential alternative treatment pathways include revascularization before TAVR, concomitant TAVR and percutaneous coronary intervention, percutaneous coronary intervention after TAVR and deferred percutaneous coronary intervention or hybrid procedures. Selection depends on underlying disease severity, antithrombotic treatment strategies, clinical presentation, and symptom evolution after TAVR. In patients undergoing surgical aortic valve replacement, the addition of coronary artery bypass grafting has been associated with improved long-term mortality, especially if CAD is complex. although it is associated with higher periprocedural risk. The therapeutic impact of percutaneous coronary intervention in patients with TAVR is less well-established. The multitude of clinical permutations and remaining uncertainties do not support a uniform treatment strategy for patients with AS and CAD. Therefore, to provide the best possible care for each individual patient, heart teams need to be familiar with the available data on AS and CAD. Herein, we provide an in-depth review of the evidence supporting the decision-making process between transcatheter and surgical approaches and the key elements of treatment selection in patients with AS and CAD., Competing Interests: Dr Windecker reports research and educational grants to the institution from Abbott, Amgen, AstraZeneca, BMS, Bayer, Biotronik, Boston Scientific, Cardinal Health, CardioValve, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Johnson & Johnson, Medicure, Medtronic, Novartis, Polares, OrPha Suisse, Pfizer, Regeneron, Sanofi-Aventis, Sinomed, Terumo, and V-Wave. Dr Windecker serves as unpaid advisory board member or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, Med Alliance, Medtronic, Novartis, Polares, Sinomed, V-Wave, and Xeltis, but has not received personal payments by pharmaceutical companies or device manufacturers. He is also member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr Reineke reports travel expenses from Abbott, Edwards Lifesciences, and Medtronic and has proctor and consulting contracts with Abbott and Medtronic. Dr Lanz reports speaker fees to the institution from Edwards Lifesciences and Abbott. Dr De Backer reports institutional research grants and personal consulting fees from Abbott, Boston Scientific, and Medtronic. Dr Borger reports that his hospital receives speakers’ honoraria or consulting fees on his behalf from Edwards Lifesciences, Medtronic, Abbott, and Artivion. Dr Pilgrim reports research grants to the institution from Edwards Lifesciences, Boston Scientifc, Biotronik, Medtronic, and Abbott, and personal fees from Biotronik and HighLife SAS. The other authors report no conflicts.

Keywords: acute coronary syndrome; myocardial infarction; troponin I EN acute coronary syndrome myocardial infarction troponin I 447 449 3 02/09/23 20230131 NES 230131 BHF Centre for Cardiovascular Science (A.B. K.K.L. A.A. A.R.C. C.T. D.E.N. N.L.M. D.M.K.), University of Edinburgh, United Kingdom. Overall, more patients had myocardial infarction ruled out by the pathway in the unselected cohort than in the selected cohort (77% [958/1242] versus 66% [1119/1695]; P<0.001),>Figure). Performance... Our findings highlight that the performance of early rule-out pathways for acute myocardial infarction that have been developed in selected patient cohorts are likely to differ substantially when applied in clinical practice because of the lower prevalence of myocardial infarction. [Extracted from the article]

BackgroundTremendous advances have occurred in therapies for peripheral vascular disease (PVD); until recently, however, it has not been possible to examine the entire clinical trial portfolio of studies for the treatment of PVD (both arterial and venous disease).Methods and resultsWe examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower-extremity peripheral artery disease and acute stroke (35% and 24%, respectively), whereas most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients >65 years of age. Enrollment in at least 1 US site decreased from 51% of trials in 2007 to 41% in 2010. Compared with noncardiology disciplines, PVD trials were more likely to be double-blinded, to investigate the use of devices and procedures, and to have industry sponsorship and assumed funding source, and they were less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas.ConclusionsPVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD.

There is a lack of consensus on how we define heart failure with preserved ejection fraction (HFpEF), with wide variation in diagnostic criteria across society guidelines. This lack of uniformity in disease definition stems in part from an incomplete understanding of disease pathobiology, phenotypic heterogeneity, and natural history. We review current knowledge gaps and existing diagnostic tools and algorithms. We present a simple approach to implement these tools within the constraints of the current knowledge base, addressing separately (1) hospitalized individuals with rest congestion, where diagnosis is more straightforward; and (2) individuals with exercise intolerance, where diagnosis is more complex. Here, a potential role for advanced or provocative testing, including evaluation of hemodynamic responses to exercise is considered. More importantly, we propose focus areas for future studies to develop accurate and feasible diagnostic tools for HFpEF, including animal models that recapitulate human HFpEF, and human studies that both address a fundamental understanding of HFpEF pathobiology, and new diagnostic approaches and tools, as well. In sum, there is an urgent need to more accurately define the syndrome of HFpEF to inform diagnosis, patient selection for clinical trials, and, ultimately, future therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is the leading cause of death among women worldwide, yet, women have historically been underrepresented in cardiovascular trials.Methods: We systematically assessed the participation of women in completed cardiovascular trials registered in ClinicalTrials.gov between 2010 and 2017, and extracted publicly available information including disease type, sponsor type, country, trial size, intervention type, and the demographic characteristics of trial participants. We calculated the female-to-male ratio for each trial and determined the prevalence-adjusted estimates for participation of women by dividing the percentage of women among trial participants by the percentage of women in the disease population (participation prevalence ratio; a ratio of 0.8 to 1.2 suggests comparable prevalence and good representation).Results: We identified 740 completed cardiovascular trials including a total of 862 652 adults, of whom 38.2% were women. The median female-to-male ratio of each trial was 0.51 (25th quartile, 0.32; 75th quartile, 0.90) overall and varied by age group (1.02 in ≤55 year old group versus 0.40 in the 61- to 65-year-old group), type of intervention (0.44 for procedural trials versus 0.78 for lifestyle intervention trials), disease type (0.34 for acute coronary syndrome versus 3.20 for pulmonary hypertension), region (0.45 for Western Pacific versus 0.55 for the Americas), funding/sponsor type (0.14 for government-funded versus 0.73 for multiple sponsors), and trial size (0.56 for smaller [n≤47] versus 0.49 for larger [n≥399] trials). Relative to their prevalence in the disease population, participation prevalence ratio was higher than 0.8 for hypertension, pulmonary arterial hypertension and lower (participation prevalence ratio 0.48 to 0.78) for arrhythmia, coronary heart disease, acute coronary syndrome, and heart failure trials. The most recent time period (2013 to 2017) saw significant increases in participation prevalence ratios for stroke (P=0.007) and heart failure (P=0.01) trials compared with previous periods.Conclusions: Among cardiovascular trials in the current decade, men still predominate overall, but the representation of women varies with disease and trial characteristics, and has improved in stroke and heart failure trials. [ABSTRACT FROM AUTHOR]

Background: Septal activation in patients with left bundle-branch block (LBBB) patterns has not been described previously. We performed detailed intracardiac mapping of left septal conduction to assess for the presence and level of complete conduction block (CCB) in the His-Purkinje system. Response to His bundle pacing was assessed in patients with and without CCB in the left bundle.Methods: Left septal mapping was performed with a linear multielectrode catheter in consecutive patients with LBBB pattern referred for device implantation (n=38) or substrate mapping (n=47). QRS width, His duration, His-ventricular (HV) intervals, and septal conduction patterns were analyzed. The site of CCB was localized to the level of the left-sided His fibers (left intrahisian) or left bundle branch. Patients with ventricular activation preceded by Purkinje potentials were categorized as having intact Purkinje activation.Results: A total of 88 left septal conduction recordings were analyzed in 85 patients: 72 LBBB block pattern and 16 controls (narrow QRS, n=11; right bundle-branch block, n=5). Among patients with LBB block pattern, CCB within the proximal left conduction system was observed in 64% (n=46) and intact Purkinje activation in the remaining 36% (n=26). Intact Purkinje activation was observed in all controls. The site of block in patients with CCB was at the level of the left His bundle in 72% and in the proximal left bundle branch in 28%. His bundle pacing corrected wide QRS in 54% of all patients with LBBB pattern and 85% of those with CCB (94% left intrahisian, 62% proximal left bundle-branch). No patients with intact Purkinje activation demonstrated correction of QRS with His bundle pacing. CCB showed better predictive value (positive predictive value 85%, negative predictive value 100%, sensitivity 100%) than surface ECG criteria for correction with His bundle pacing.Conclusions: Heterogeneous septal conduction was observed in patients with surface LBBB pattern, ranging from no discrete block to CCB. When block was present, we observed pathology localized within the left-sided His fibers (left intrahisian block), which was most amenable to corrective His bundle pacing by recruitment of latent Purkinje fibers. ECG criteria for LBBB incompletely predicted CCB, and intracardiac data might be useful in refining patient selection for resynchronization therapy. [ABSTRACT FROM AUTHOR]

Keywords: heart failure; heart valve diseases EN heart failure heart valve diseases 2482 2484 3 12/23/20 20201222 NES 201222 Although addressing the same issue, the MITRA-FR trial (Percutaneous Repair With the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) and the COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) led to divergent results.[1],[2] Differences in patient characteristics may account for these discrepancies but have not been specifically studied. Characteristics and Outcome of COAPT-Eligible and -Ineligible MITRA-FR Patients and Corresponding Characteristics of COAPT Patients In the intention-to-treat analysis, overall, the composite efficacy end point occurred in 121 (64.0%) COAPT-eligible patients and 57 (74.0%) COAPT-ineligible patients (unadjusted hazard ratio [HR], 0.80 [95% CI, 0.58-1.11]). Although a majority of MITRA-FR patients were deemed COAPT eligible, they presented markedly different baseline characteristics versus patients of the COAPT trial. [Extracted from the article]

In patients with stable coronary artery disease, percutaneous coronary intervention is associated with improved outcomes if the lesion is deemed significant by invasive functional assessment using fractional flow reserve. Recent studies have shown that a revascularization strategy using instantaneous wave-free ratio is noninferior to fractional flow reserve in patients with intermediate-grade stenoses. The decision to perform coronary artery bypass grafting surgery is usually based on anatomic assessment of stenosis severity by coronary angiography. The data on the role of invasive functional assessment in guiding surgical revascularization are limited. In this review, we discuss the diagnostic and prognostic significance of invasive functional assessment in patients considered for coronary artery bypass grafting. In addition, we critically discuss ongoing and future clinical trials on the role of invasive functional assessment in surgical revascularization. [ABSTRACT FROM AUTHOR]

Background: The dual antiplatelet therapy (DAPT) score was developed to estimate ischemic and bleeding risks from the DAPT study. However, few studies validated its utility externally. We sought to validate the utility of the DAPT score in the Japanese population.Methods: In a pooled cohort of 3 studies conducted in Japan (the CREDO-Kyoto [Coronary Revascularization Demonstrating Outcome Study in Kyoto] Registry Cohort-2, RESET [Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial], and NEXT [NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial]), we compared risks for ischemic and bleeding events from 13 to 36 months after percutaneous coronary intervention among patients with a DAPT score ≥2 (high DS) and a DAPT score <2 (low DS).Results: Among 12 223 patients receiving drug-eluting stents who were free from ischemic or bleeding events at 13 months after percutaneous coronary intervention, 3944 patients had high DS and 8279 had low DS. The cumulative incidence of primary ischemic end point (myocardial infarction/stent thrombosis) was significantly higher in high DS than in low DS (1.5% versus 0.9%, P=0.002), whereas the cumulative incidence of primary bleeding end point (GUSTO moderate/severe) tended to be lower in high DS than in low DS (2.1% versus 2.7%, P=0.07). The cumulative incidences of cardiac death, myocardial infarction, and stent thrombosis were also significantly higher in high DS than in low DS (2.0% versus 1.4%, P=0.03; 1.5% versus 0.8%, P=0.002; 0.7% versus 0.3%, P<0.001, respectively), whereas the cumulative incidences of noncardiac death and GUSTO severe bleeding were significantly lower in high DS than in low DS (2.4% versus 3.9%, P<0.001; 1.0% versus 1.6%, P=0.03, respectively).Conclusions: In the current population, the DAPT score successfully stratified ischemic and bleeding risks, although the ischemic event rate was remarkably low even in high DS. Further studies would be warranted to evaluate the utility of prolonged DAPT guided by the DAPT score. [ABSTRACT FROM AUTHOR]

Background: In the event of rupture of an abdominal aortic aneurysm (AAA), mortality is very high. AAA prevalence and incidence of ruptures have been reported to be decreasing. The treatment of AAA has also undergone a change in recent decades with a shift toward endovascular aneurysm repair (EVAR). Our aim was to evaluate how these changes have affected the elective and emergency treatment of AAA and their results in Finland.Methods: All patients treated for AAA in Finland, a country with a population of 5.5 million, during 2000 to 2014 were searched from the registry of the Finnish Institute for Health and Welfare. Data on all patients who had died of AAA during the same time period were obtained from Statistics Finland. The data were combined and analyzed.Results: The annual incidence of ruptured AAA was 16.4 per 100 000 population over 50 years and decreased significantly during the study period. Over half of the 4949 patients who had a ruptured AAA died outside the hospital. Thirty-day mortality after emergency repair was 39.4%. Intact AAA repairs numbered 4956. The absolute number of annual repairs increased during the study period, and the use of EVAR became the dominant method of elective repair. Thirty-day mortality in elective AAA repair dropped significantly from 6.3% in 2000 to 2004 to 2.7% in 2010 to 2014 mostly because of the increased number of EVAR procedures with lower mortality. Long-term mortality in patients treated with EVAR was higher than in patients treated with open repair. Mortality after elective AAA repair was primarily attributable to cardiovascular causes, but there was a slightly higher proportion of AAA-related late deaths in patients treated with EVAR.Conclusions: Ruptured AAA incidence for men >65 years has declined by nearly 30% in Finland, likely because of the decrease in AAA prevalence. The treatment results have improved as well for both elective and emergency repair. Increased use of EVAR has resulted in a decrease of mortality after elective AAA repair, but results of open repair have improved as well. However, late mortality from elective EVAR is surprisingly high in comparison with open repair, which may have been exaggerated by patient selection. [ABSTRACT FROM AUTHOR]

Cardiogenic shock is a high-acuity, potentially complex, and hemodynamically diverse state of end-organ hypoperfusion that is frequently associated with multisystem organ failure. Despite improving survival in recent years, patient morbidity and mortality remain high, and there are few evidence-based therapeutic interventions known to clearly improve patient outcomes. This scientific statement on cardiogenic shock summarizes the epidemiology, pathophysiology, causes, and outcomes of cardiogenic shock; reviews contemporary best medical, surgical, mechanical circulatory support, and palliative care practices; advocates for the development of regionalized systems of care; and outlines future research priorities. [ABSTRACT FROM AUTHOR]

Severe mitral regurgitation is a common and complex disease that is associated with an adverse prognosis. For decades, surgical treatment has been the standard of care. Recently, multiple technologies for transcatheter mitral therapy have emerged, with the potential for both repair and replacement in patients with native mitral regurgitation. Transcatheter mitral technologies have potential as solutions for unmet clinical needs. Further rigorous clinical studies are needed to determine their efficacy and safety, as well as the appropriate patient candidates. These evaluations will help to define the role of transcatheter mitral therapy as a potentially exciting new strategy to improve the lives of patients with mitral regurgitation. [ABSTRACT FROM AUTHOR]

Background -The genotype-phenotype correlation of SCN5A mutations as a predictor of cardiac events in Brugada syndrome remains controversial. We aimed to establish a registry limited to probands, with a long follow-up period, so that the genotype-phenotype correlation of SCN5A mutations in Brugada syndrome can be examined without patient selection bias. Methods -This multicenter registry enrolled 415 probands (n=403; men, 97%; age, 46±14 years) diagnosed with Brugada syndrome whose SCN5A gene was analyzed for mutations. Results -During a mean follow-up period of 72 months, the overall cardiac event rate was 2.5%/year. Compared with probands without mutations (SCN5A (-), n=355), probands with SCN5A mutations (SCN5A(+), n=60) experienced their first cardiac event at a younger age (34 vs. 42 years, P=0.013), had a higher positive rate of late potentials (89% vs. 73%, P=0.016), exhibited longer P-wave, PQ, and QRS durations, and had a higher rate of cardiac events (P=0.017 by log-rank). Multivariate analysis indicated that only SCN5A mutation and history of aborted cardiac arrest were significant predictors of cardiac events (SCN5A(+) vs. SCN5A(-): hazard ratio, 2.0 and P=0.045; history of aborted cardiac arrest vs. no such history: hazard ratio, 6.5 and P<0.001). Conclusions -Brugada syndrome patients with SCN5A mutations exhibit more conduction abnormalities on electrocardiogram and have higher risk for cardiac events. [ABSTRACT FROM AUTHOR]

Functional tricuspid regurgitation (FTR) is common, whether in association with mitral or aortic valve disease or presenting as an isolated valvular disease. Several studies have shown that TR is associated with poor patient outcomes, though a cause-and-effect relationship of TR to mortality has not been proven. Similarly the impact of surgical treatment of TR on outcomes needs well-controlled randomized trials that are under planning. The current professional society guidelines for treatment of TR are based on expert opinions with a level of evidence C for all indications. Transcatheter therapies for valvular heart disease are often based on established surgical techniques. When surgical therapy has well studied benefits including a reduction in mortality (e.g. aortic valve replacement for aortic stenosis), percutaneous therapies can be compared to surgery with survival as an endpoint. Similarly, the safety of surgical therapies (e.g. surgical aortic valve replacement) can serve as a benchmark for the safety of percutaneous treatment. In establishing percutaneous treatments for TR, on the other hand, there are several challenges: 1) the severity of TR and RV dysfunction are often difficult to determine; 2) the impact of TR on mortality or heart failure outcomes is not as clearly defined; and 3) surgical treatments are multiple without robust data for indications and outcomes. Importantly, the US Food and Drug Administration (FDA) is interested in providing expedited access for devices that fill an unmet clinical need by demonstrating appropriate intermediate and surrogate endpoints. Therefore, the aforementioned challenges also present opportunities to better define how trials for percutaneous treatments of TR can be conducted as we move forward (Table). [ABSTRACT FROM AUTHOR]

Keywords: cardiovascular risk; computed tomography; coronary artery disease EN cardiovascular risk computed tomography coronary artery disease 585 586 2 08/22/22 20220823 NES 220823 According to the American Heart Association (AHA) and the American College of Cardiology (ACC), coronary artery calcium (CAC) scanning is the best way to improve selection of patients for lipid-lowering drug treatment when the initial risk assessment by the Pooled Cohort Equations is inconclusive.[1] Similar recommendations have been issued by the Canadian Cardiovascular Society and the Cardiac Society of Australia and New Zealand. Cardiology organizations have recommended CAC as a reasonable test in intermediate risk primary prevention patients to improve selection of patients for more intensive and safe statin therapy for prevention. [Extracted from the article]

The article projects the future of cardiovascular (CV) medicine clinical trials in the U.S. Topics discussed include an overview of the clinical trials in CV medicine, the CV safety trials, the improvements in CV patient selection, the increased cost of CV clinical trials, and the concepts and design of CV trials.

Background: Surgery for severe mitral regurgitation is indicated if symptoms or left ventricular dilation or dysfunction occur. However, prognosis is already reduced by this stage, and earlier surgery on asymptomatic patients has been advocated if valve repair is likely, but identifying suitable patients for early surgery is difficult. Quantifying the regurgitation may help, but evidence for its link with outcome is limited. Cardiovascular magnetic resonance (CMR) can accurately quantify mitral regurgitation, and we examined whether this was associated with the future need for surgery. Methods and Results: One hundred nine asymptomatic patients with echocardiographic moderate or severe mitral regurgitation had baseline CMR scans and were followed up for up to 8 years (mean, 2.5±1.9 years). CMR quantification accurately identified patients who progressed to symptoms or other indications for surgery: 91% of subjects with regurgitant volume ≤55 mL survived to 5 years without surgery compared with only 21% with regurgitant volume >55 mL (P<0.0001). A similar separation was observed for regurgitant fraction ≤40% and >40%. CMR-derived end-diastolic volume index showed a weaker association with outcome (proportions surviving without surgery at 5 years, 90% for left ventricular end-diastolic volume index <100 mL/m(2) versus 48% for ≥100 mL/m(2)) and added little to the discriminatory power of regurgitant fraction/volume alone. Conclusions: CMR quantification of mitral regurgitation was associated with the development of symptoms or other indications for surgery and showed better discriminatory ability than the reference-standard CMR-derived ventricular volumes. CMR may be able to identify appropriate patients for early surgery, with the potential to change clinical practice, although the clinical benefits of early surgery require confirmation in a clinical trial. [ABSTRACT FROM AUTHOR]

Background: Representation by age ensures appropriate translation of clinical trial results to practice, but, historically, older patients have been underrepresented in clinical trial populations. As the general population has aged, it is unknown whether clinical trial enrollment has changed in parallel. Methods and Results: We studied time trends in enrollment, clinical characteristics, treatment, and outcomes by age among 76 141 patients with non-ST-segment-elevation acute coronary syndrome enrolled in 11 phase III clinical trials over 17 years (1994-2010). Overall, 19.7% of patients were ≥75 years; this proportion increased from 16% during 1994 to 1997 to 21% during 1998 to 2001 and 23.2% during 2002 to 2005, but declined to 20.2% in 2006 to 2010. The number of comorbidities increased with successive time periods irrespective of age. There were substantial increases in the use of evidence-based medication in-hospital and at discharge regardless of age. Although predicted 6-month mortality increased slightly over time, observed 6-month mortality declined significantly in all age strata (1994-1997 versus 2006-2010: <65 years: 3.0% versus 1.9%; 65-74 years: 7.5% versus 3.4%; 75-79 years: 13.0% versus 6.5%; 80-84 years: 17.6% versus 8.2%; and ≥85 years: 24.8% versus 12.6%). Conclusions: The distribution of enrollment by age in phase III non-ST-segment-elevation acute coronary syndrome trials was unchanged over time. Irrespective of age, post-myocardial infarction mortality decreased significantly over time, concurrent with increased evidence-based care and despite increasing comorbidities. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00089895. [ABSTRACT FROM AUTHOR]

The article discusses the limits for Extracorporeal Cardiopulmonary Resuscitation (ECPR) which is the emergent application of extracorporeal membrane oxygenation (ECMO) during active cardiopulmonary resuscitation (CPR). Topics include ECPR as a time-limited resuscitative treatment that must end when it is apparent that efforts have failed to achieve the goal of survival independent of life support.

The article focuses on a study based on randomized controlled trials of percutaneous transcatheter closure of a patent foramen ovale (PFO) in patients with cryptogenic ischemic stroke that has reported a reduction in recurrent ischemic stroke with PFO closure, medical therapy versus medical therapy alone. It mentions need for establishing a clinical diagnosis of stroke and to confirm that the pathological type is ischemic by early brain imaging before selecting patients for PFO closure.

The article offers information about implementing ventricular tachycardia (VT) ablation in patients with heart disease and with implantable cardioverter defibrillators. It reports that such life-saving therapies do not prevent arrhythmia recurrences and presents randomized trials which demonstrated the efficacy of both sotalol and amiodarone in reducing VT recurrences.

The article focuses on the "DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo" study, also known as the DAWN study. Topics discussed include the criteria to the selection of patients that may benefit from mechanical thrombectomy, the impact of the study on acute stroke therapy, and its implications for many healthcare providers and emergency medical services (EMS) systems.

The article discuses new challenges and opportunities associated with Acute Coronary Syndromes (ACS) after completion of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) Trial. Topics ddiscussedinclude inflammation as a new therapeutic target in the treatment of ischemic heart disease, new pharmacological targets in the inflammatory pathways and identification of new therapeutic targets in patients with ACS.

Over the past decade, personalized medicine has received considerable attention from researchers, drug developers, and regulatory agencies. Personalized medicine includes identifying patients most likely to benefit and those most likely to experience adverse reactions in response to a drug, and tailoring therapy based on pharmacokinetics or pharmacodynamic response, as well. Perhaps most exciting is finding ways to identify likely responders through genetic, proteomic, or other tests, so that only likely responders will be treated. However, less precise methods such as identifying historical, demographic, or other indicators of increased or reduced responsiveness are also important aspects of personalized medicine. The cardiovascular field has not used many genetic or proteomic markers, but has regularly used prognostic variables to identify likely responders. The development of biomarker-based approaches to personalized medicine in cardiovascular disease has been challenging, in part, because most cardiovascular therapies treat acquired syndromes, such as acute coronary syndrome and heart failure, which develop over many decades and represent the end result of several pathophysiological mechanisms. More precise disease classification and greater understanding of individual variations in disease pathology could drive the development of targeted therapeutics. Success in designing clinical trials for personalized medicine will require the selection of patient populations with attributes that can be targeted or that predict outcome, and the use of appropriate enrichment strategies once such attributes are identified. Here, we describe examples of personalized medicine in cardiovascular disease, discuss its impact on clinical trial design, and provide insight into the future of personalized cardiovascular medicine from a regulatory perspective. [ABSTRACT FROM AUTHOR]

Background--It is unknown whether the appropriate use of percutaneous coronary intervention (PCI) has improved over time and whether trends in PCI appropriateness have been accompanied by changes in the use of PCI. Methods and Results--We applied appropriate use criteria to determine the appropriateness of all 51 872 PCI performed in Washington State from 2010 through 2013. We evaluated the number of PCIs performed from 2006 through 2013 to provide a comparator period that preceded statewide appropriateness assessment beginning in 2010. Between 2010 and 2013, the overall number of PCI decreased by 6.8% (13 267 PCIs in 2010 to 12 193 in 2013) with a 43% decline in the number of PCIs for elective indications (3818 PCIs in 2010 to 2193 PCIs in 2013). The decline in the use of elective PCI was significantly larger after the onset of statewide PCI appropriateness assessment in 2010 (P=0.03). The proportion of elective PCIs classified as appropriate increased from 26% in 2010 to 38% in 2013, whereas the proportion of inappropriate PCIs decreased from 16% to 13% (P<0.001 for trends). Significant improvements in the proportion of inappropriate PCI were limited to the tertile of hospitals with the largest decline in PCIs classified as inappropriate (25% in 2010 to 12% in 2013; P=0.03). Conclusions--In Washington State, the use of PCI for elective indications has decreased over time with concurrent improvements in PCI appropriateness. However, improvements in PCI appropriateness were limited to a minority of hospitals. Understanding processes at these high-performing hospitals may inform efforts to improve PCI appropriateness. [ABSTRACT FROM AUTHOR]

The article discusses the need for a uniform methodological approach to cost effectiveness research for heart assist device in the U.S. It notes that a favorable impact on therapy cost can result from refinements in patient selection and renewed focus on patient care processes. It mentions that mechanical circulatory support can influence affordability of devices.

The article discusses why left ventricular assist device (LVAD) should not be considered as standard of care for patients with advanced heart failure (HF) who are not qualified for heart transplantation. It mentions the lack of long-term survival data with permanent VASDs and underdevelopment of patient selection criteria to warrant the designation of VADs as second-line therapy . The authors note that designating permanent LVAD as standard second-line therapy would be reckless and ill advised.

The article discusses whether left ventricular assist devices (LVADs) can be considered as standard of care for refractory heart failure patients not qualified for transplantation. It explores the developments and advances in mechanical circulation support (MCS) systems and the recognition of LVAD therapy for patient ineligible for transplantation. It suggests that the developments in MCS will shape the framework of the standard of care in patients with advanced refractory heart failure.