Background Cardiovascular risk models remain incomplete. Small-molecule metabolites may reflect underlying disease and, as such, serve as novel biomarkers of cardiovascular risk. Methods We studied ...2,023 consecutive patients undergoing cardiac catheterization. Mass spectrometry profiling of 69 metabolites and lipid assessments were performed in fasting plasma. Principal component analysis reduced metabolites to a smaller number of uncorrelated factors. Independent relationships between factors and time-to-clinical events were assessed using Cox modeling. Clinical and metabolomic models were compared using log-likelihood and reclassification analyses. Results At median follow-up of 3.1 years, there were 232 deaths and 294 death/myocardial infarction (MI) events. Five of 13 metabolite factors were independently associated with mortality: factor 1 (medium-chain acylcarnitines: hazard ratio HR 1.12 95% CI, 1.04-1.21, P = .005), factor 2 (short-chain dicarboxylacylcarnitines: HR 1.17 1.05-1.31, P = .005), factor 3 (long-chain dicarboxylacylcarnitines: HR 1.14 1.05-1.25, P = .002); factor 6 (branched-chain amino acids: HR 0.86 0.75-0.99, P = .03), and factor 12 (fatty acids: HR 1.19 1.06-1.35, P = .004). Three factors independently predicted death/MI: factor 2 (HR 1.11 1.01-1.23, P = .04), factor 3 (HR 1.13 1.04-1.22, P = .005), and factor 12 (HR 1.18 1.05-1.32, P = .004). For mortality, 27% of intermediate-risk patients were correctly reclassified (net reclassification improvement 8.8%, integrated discrimination index 0.017); for death/MI model, 11% were correctly reclassified (net reclassification improvement 3.9%, integrated discrimination index 0.012). Conclusions Metabolic profiles predict cardiovascular events independently of standard predictors.
Randomized clinical trials provide the foundation of clinical evidence to guide physicians in their selection of treatment options. Importantly, randomization is the only reliable method to control ...for confounding factors when comparing treatment groups. However, randomized trials have limitations, including the increasingly prohibitive costs of conducting adequately powered studies. Local and national regulatory requirements, delays in approval, and unnecessary trial processes have led to increased costs and decreased efficiency. Another limitation is that clinical trials involve selected patients who are treated according to protocols that might not represent real-world practice. A possible solution is registry-based randomized clinical trials. By including a randomization module in a large inclusive clinical registry with unselected consecutive enrolment, the advantages of a prospective randomized trial can be combined with the strengths of a large-scale all-comers clinical registry. We believe that prospective registry-based randomized clinical trials are a powerful tool for conducting studies efficiently and cost-effectively.
Medication adherence: A call for action Bosworth, Hayden B., PhD; Granger, Bradi B., RN, PhD; Mendys, Phil, Pharm D ...
The American heart journal,
09/2011, Volume:
162, Issue:
3
Journal Article
Peer reviewed
Open access
Poor adherence to efficacious cardiovascular-related medications has led to considerable morbidity, mortality, and avoidable health care costs. This article provides results of a recent think-tank ...meeting in which various stakeholder groups representing key experts from consumers, community health providers, the academic community, decision-making government officials (Food and Drug Administration, National Institutes of Health, etc), and industry scientists met to evaluate the current status of medication adherence and provide recommendations for improving outcomes. Below, we review the magnitude of the problem of medication adherence, prevalence, impact, and cost. We then summarize proven effective approaches and conclude with a discussion of recommendations to address this growing and significant public health issue of medication nonadherence.
Summary In patients with non-valvular atrial fibrillation, oral anticoagulation with vitamin K antagonists reduces the risk of stroke by more than 60%. But vitamin K antagonists have limitations, ...including causing serious bleeding such as intracranial haemorrhage and the need for anticoagulation monitoring. In part related to these limitations, they are used in only about half of patients who should be treated according to guideline recommendations. In the past decade, oral agents have been developed that directly block the activity of thrombin (factor IIa), as well as drugs that directly inhibit activated factor X (Xa), which is the first protein in the final common pathway to the activation of thrombin. These novel non-vitamin K antagonist oral anticoagulants (NOACs) have been shown to be at least as good as warfarin for stroke prevention in atrial fibrillation and they have proved to have better safety profiles. Their net advantage is underscored by significantly lower all-cause mortality compared with warfarin in large clinical trials. Because of these features and their ease of use, they are recommended for stroke prevention in atrial fibrillation. They have also a fast onset and offset of action, but they currently lack specific antidotes. This paper addresses the role of anticoagulation for stroke prevention in atrial fibrillation in the era of NOACs, with a focus on special situations including management in the event of bleeding and around the time of procedures including cardioversion, catheter ablation, and device implantation. Also their use in patients with concomitant coronary artery disease, with advanced age, with chronic kidney disease, or with valvular heart disease will be discussed as well as the interaction of NOACs with other cardiac medication, and switching between anticoagulants.
Microvascular obstruction (MVO) is the underlying cause for the no-reflow phenomenon in ST-segment elevation myocardial infarction (STEMI). The association between MVO assessed by cardiac magnetic ...resonance imaging (CMR) and prognosis has not been convincingly demonstrated. We sought to determine the relationship between MVO assessed early after primary percutaneous coronary intervention (PCI) in STEMI and all-cause mortality, hospitalization for heart failure (HF), and reinfarction.
We performed a pooled analysis using individual patient data from seven randomized primary PCI trials in which MVO was assessed within 7 days after reperfusion by CMR using late gadolinium enhancement imaging (n = 1688). Clinical follow-up was performed for at least 6 months after the index event. Median time to CMR after STEMI was 3 days interquartile range (IQR) 2-4, and median duration of clinical follow-up was 365 days (IQR 188-374). Microvascular obstruction was present in 960 (56.9%) of patients, and median MVO (percent left ventricular myocardial mass) was 0.47% (IQR 0.00-2.54). A graded response was present between the extent of MVO (per 1.0% absolute increase) and subsequent mortality Cox adjusted hazard ratio (HR) 1.14, 95% confidence interval (CI) 1.09-1.19, P < 0.0001 and hospitalization for HF (Cox adjusted HR 1.08, 95% CI 1.05-1.12, P < 0.0001). Microvascular obstruction remained significantly associated with all-cause mortality even after further adjustment for infarct size (Cox adjusted HR 1.09, 95% CI 1.01-1.17, P = 0.03). MVO was not significantly related to subsequent reinfarction (P = 0.29).
The presence and extent of MVO measured by CMR after primary PCI in STEMI are strongly associated with mortality and hospitalization for HF within 1 year.
Post-Myocardial Infarction Heart Failure Bahit, M. Cecilia; Kochar, Ajar; Granger, Christopher B.
JACC. Heart failure,
March 2018, 2018-03-00, 20180301, Volume:
6, Issue:
3
Journal Article
Peer reviewed
Open access
Heart failure (HF) complicating myocardial infarction (MI) is common and may be present at admission or develop during the hospitalization. Among patients with MI, there is a strong relationship ...between degree of HF and mortality. The optimal management of the patient with HF complicating MI varies according to time since the onset of infarction. Medical therapy for HF after MI includes early (within 24 h) initiation of angiotensin-converting enzyme inhibitors and early (within 7 days) use of aldosterone antagonists. Alternatively, in patients with MI and ongoing HF, early use (<24 h) of beta-blockers is associated with an increased risk of cardiogenic shock and death. Long-term beta-blocker use after MI is associated with a reduced risk of reinfarction and death. Thus, it is critical to frequently re-evaluate beta-blocker eligibility among patients after MI with HF. Cardiogenic shock is an extreme presentation of HF after MI and is a leading cause of death in the MI setting. The only therapy proven to reduce mortality for patients with cardiogenic shock is early revascularization. Several studies are examining new approaches to mitigate the occurrence and adverse impact of post-MI HF. These studies are testing drugs for HF and diabetes and are evaluating mechanical support devices to bridge patients to recovery or transplantation.
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Coronary Artery Disease in Patients ≥80 Years of Age Madhavan, Mahesh V.; Gersh, Bernard J.; Alexander, Karen P. ...
Journal of the American College of Cardiology,
05/2018, Volume:
71, Issue:
18
Journal Article
Peer reviewed
Open access
Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients ≥80 years of age. Nonetheless, older patients have typically been under-represented in cardiovascular clinical ...trials. Understanding the pathophysiology, epidemiology, and optimal means of diagnosis and treatment of CAD in older adults is crucial to improving outcomes in this high-risk population. A patient-centered approach, taking into account health status, functional ability and frailty, cognitive skills, and patient preferences is essential when caring for older adults with CAD. The present systematic review focuses on the current knowledge base, gaps in understanding, and directions for future investigation pertaining to CAD in patients ≥80 years of age.
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Summary Cryptogenic (of unknown cause) ischaemic strokes are now thought to comprise about 25% of all ischaemic strokes. Advances in imaging techniques and improved understanding of stroke ...pathophysiology have prompted a reassessment of cryptogenic stroke. There is persuasive evidence that most cryptogenic strokes are thromboembolic. The thrombus is thought to originate from any of several well established potential embolic sources, including minor-risk or covert cardiac sources, veins via paradoxical embolism, and non-occlusive atherosclerotic plaques in the aortic arch, cervical, or cerebral arteries. Accordingly, we propose that embolic strokes of undetermined source are a therapeutically relevant entity, which are defined as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources, with a clear indication for anticoagulation. Because emboli consist mainly of thrombus, anticoagulants are likely to reduce recurrent brain ischaemia more effectively than are antiplatelet drugs. Randomised trials testing direct-acting oral anticoagulants for secondary prevention of embolic strokes of undetermined source are warranted.
Smartwatch and fitness band wearable consumer electronics can passively measure pulse rate from the wrist using photoplethysmography (PPG). Identification of pulse irregularity or variability from ...these data has the potential to identify atrial fibrillation or atrial flutter (AF, collectively). The rapidly expanding consumer base of these devices allows for detection of undiagnosed AF at scale.
The Apple Heart Study is a prospective, single arm pragmatic study that has enrolled 419,093 participants (NCT03335800). The primary objective is to measure the proportion of participants with an irregular pulse detected by the Apple Watch (Apple Inc, Cupertino, CA) with AF on subsequent ambulatory ECG patch monitoring. The secondary objectives are to: 1) characterize the concordance of pulse irregularity notification episodes from the Apple Watch with simultaneously recorded ambulatory ECGs; 2) estimate the rate of initial contact with a health care provider within 3 months after notification of pulse irregularity. The study is conducted virtually, with screening, consent and data collection performed electronically from within an accompanying smartphone app. Study visits are performed by telehealth study physicians via video chat through the app, and ambulatory ECG patches are mailed to the participants.
The results of this trial will provide initial evidence for the ability of a smartwatch algorithm to identify pulse irregularity and variability which may reflect previously unknown AF. The Apple Heart Study will help provide a foundation for how wearable technology can inform the clinical approach to AF identification and screening.
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