- Correlates of Echocardiographic Indices of Cardiac Remodeling Over the Adult Life Course: Longitudinal Observations From the Framingham Heart Study
- Hypertension in Pregnancy and Later Cardiovascular Risk: Common Antecedents?
- Improving Evidence-Based Care for Heart Failure in Outpatient Cardiology Practices: Primary Results of the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF)
- Pathogenesis of Sudden Unexpected Death in a Clinical Trial of Patients With Myocardial Infarction and Left Ventricular Dysfunction, Heart Failure, or Both
- Cardiac Positron Emission Tomography/Computed Tomography Imaging Accurately Detects Anatomically and Functionally Significant Coronary Artery Disease
- First Clinical Application of an Actively Reversible Direct Factor IXa Inhibitor as an Anticoagulation Strategy in Patients Undergoing Percutaneous Coronary Intervention
- Differences Between Out-of-Hospital Cardiac Arrest in Residential and Public Locations and Implications for Public-Access Defibrillation
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Correlates of Echocardiographic Indices of Cardiac Remodeling Over the Adult Life Course: Longitudinal Observations From the Framingham Heart Study
The human heart undergoes dynamic, incremental alterations in structure and function over the lifespan, a phenomenon referred to as cardiac remodeling. Examination of the course and correlates of cardiac remodeling in aging adults is critical for elucidating the pathways by which older age predisposes to cardiac dysfunction, particularly heart failure, in the setting of a preserved ejection fraction. Using longitudinal data collected from participants in the Framingham Offspring Study (up to 4 serial echocardiographic observations per individual, totaling 11 485 observations) and multilevel statistical modeling, we observed that left ventricular (LV) cavity dimensions (end-systolic more than end-diastolic) decreased with advancing age, whereas LV wall thickness and fractional shortening increased. Women and individuals with diabetes mellitus experienced greater age-associated increases in LV wall thickness. However, the presence of diabetes or a higher blood pressure level was associated with a lesser decrease in LV dimensions with older age. Similarly, treatment with antihypertensive medication was a marker of an attenuated increase in fractional shortening with aging. Together, these findings indicate that cardiac remodeling over the adult life course is characterized by a distinct pattern of increasing LV wall thickness, decreasing LV dimensions, and increasing fractional shortening with advancing age. Notably, female sex, greater blood pressure load, and presence of diabetes serve to attenuate this remodeling pattern. Overall, these observations suggest a mechanism by which women with hypertension and individuals with diabetes may be particularly predisposed to heart failure with a preserved ejection fraction in later life. See p 570.
Hypertension in Pregnancy and Later Cardiovascular Risk: Common Antecedents?
Gestational hypertension and preeclampsia are common disorders in pregnancy, and both disorders have been associated with a substantially increased risk of cardiovascular disease later in life. Therefore, hypertension in pregnancy may provide a unique opportunity for the clinicians to identify women at an early stage who may be at increased risk of future cardiovascular disease. It is uncertain, however, whether the association of hypertensive pregnancy disorders with cardiovascular disease can be attributed to factors that operate in pregnancy or to prepregnancy factors that are associated with both the pregnancy condition and later cardiovascular disease. We linked data from the Medical Birth Registry of Norway to 2 waves of a large population-based health survey in Norway (the Nord-Trøndelag Health Study [HUNT]) and prospectively examined the association of hypertensive disorders in >3225 pregnancies with subsequent measurements of body mass index, blood pressure, and serum levels of high-density lipoprotein cholesterol and triglycerides; we simultaneously adjusted for prepregnancy measurements of the same factors. We found that the associations of hypertensive disorders in pregnancy with subsequent body mass index and blood lipids were considerably attenuated after adjustment for risk factors measured before pregnancy. The results of this study suggest that the positive association of preeclampsia and gestational hypertension with later unfavorable cardiovascular risk factors may be due largely to shared prepregnancy risk factors such as obesity, dyslipidemia, and elevated blood pressure rather than reflecting factors that can be attributed to the hypertensive pregnancy. See p 579.
Improving Evidence-Based Care for Heart Failure in Outpatient Cardiology Practices: Primary Results of the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF)
Heart failure (HF) is a chronic progressive disease that results in substantial morbidity, mortality, and expenditure of healthcare resources. Despite compelling scientific evidence and professional society guidelines, beneficial therapies for HF remain underused and inconsistently applied in many care settings. New, more effective approaches to improve the use of guideline-recommended therapies for HF are needed. The Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) prospectively tested a multidimensional practice-specific performance improvement intervention on the use of guideline-recommended therapies for HF in outpatient cardiology practices. Performance data were collected in a random sample of HF patients from 167 outpatient cardiology practices at baseline (pre-intervention), longitudinally following intervention at 12 and 24 months, and in unique patient cohorts at 6 and 18 months. Participants included 34 810 patients with reduced left ventricular ejection fraction and chronic HF or post–myocardial infarction. Interventions included clinical decision support tools, structured improvement strategies, and chart audits with performance feedback. The performance improvement intervention resulted in significant improvements in 5 of 7 quality measures at the 24-month assessment compared to baseline. Improvements in the unique single-point-in-time cohorts were smaller. The results of this study suggest a favorable impact of applying performance improvement techniques of clinical decision support, reminder systems, guideline-driven care improvement tools, educational outreach, collaborative support, performance profiling, and feedback in real-world cardiology practices. These findings may also help to establish a model and framework for future performance-improvement programs administered in the outpatient setting. See p 585.
Pathogenesis of Sudden Unexpected Death in a Clinical Trial of Patients With Myocardial Infarction and Left Ventricular Dysfunction, Heart Failure, or Both
Sudden unexpected death is highest in the early post–myocardial infarction period. Yet, the Defibrillator in Acute Myocardial Infarction Trial and the Immediate Risk Stratification Improves Survival Trial showed no improvement in mortality with early placement of an implantable cardioverter-defibrillator 6 to 40 days after myocardial infarction. The Optimal Trial in Myocardial Infarction With Angiotensin II Antagonist Losartan review of patients with autopsies showed that an acute myocardial infarction was found in 55% (37 of 67) of the deaths classified as sudden death. This lack of precision in classification might have serious implications. To better understand the pathophysiological events that lead to sudden unexpected death after myocardial infarction, we assessed autopsy records in a series of cases classified as sudden cardiac death in patients from the Valsartan in Acute Myocardial Infarction Trial. The present study demonstrates that recurrent myocardial infarction or myocardial rupture account for a high proportion of sudden unexpected deaths in the early period after acute myocardial infarction, whereas arrhythmic death may be more likely subsequently. These findings may help explain the lack of benefit of early implantable cardioverter-defibrillator therapy. See p 597.
Cardiac Positron Emission Tomography/Computed Tomography Imaging Accurately Detects Anatomically and Functionally Significant Coronary Artery Disease
Accurate noninvasive assessment of coronary artery disease is a challenging task. In a cohort of 107 patients at intermediate clinical risk, we measured the power of hybrid positron emission tomography and computed tomography coronary angiography against invasive coronary angiography with fractional flow reserve for the detection of obstructive coronary artery disease. Although both computed tomography angiography and positron emission tomography individually were able to rule out significant coronary artery disease (negative predictive value, 97%), both approaches showed only modest positive predictive value. Positron emission tomography perfusion imaging alone could not always separate microvascular dysfunction from epicardial stenoses, whereas computed tomography angiography was limited in defining the physiological significance of anatomic stenosis. Hybrid positron emission tomography/computed tomography significantly improved this accuracy to 98%. This was achieved with a rapid 30-minute imaging protocol with a reasonable radiation dose (<10 mSv) to the patient. These data suggest that hybrid positron emission tomography/computed tomography imaging of the heart is a feasible, accurate method to assess coronary artery disease noninvasively in a symptomatic, moderate-risk patient population. See p 603.
First Clinical Application of an Actively Reversible Direct Factor IXa Inhibitor as an Anticoagulation Strategy in Patients Undergoing Percutaneous Coronary Intervention
Anticoagulants for percutaneous coronary intervention (PCI) are limited by unpredictable pharmacodynamics and/or lack of active reversibility. The REG1 system is an oligonucleotide RNA aptamer pair comprising the direct rapid-onset factor IXa inhibitor RB006 and its active dose-dependent control agent RB007. REG1 offers effective, predictable, and reversible anticoagulation. We assessed whether anticoagulation through factor IXa inhibition with RB006 could support low- to moderate-risk PCI. This phase IIa study enrolled 26 patients undergoing elective PCI. In a roll-in group, 2 patients received REG1 and glycoprotein IIb/IIIa inhibitors. Then, 24 patients were randomized 5:1 to REG1 (n=20) or unfractionated heparin (n=4). REG1 patients received RB006 (1 mg/kg) after arterial access. In the first 10 REG1 patients, RB007 was dosed to partially reverse RB006 by 50% after PCI and to completely reverse RB006 at 4 hours. In the subsequent 10 REG1 patients, RB007 was dosed once to completely reverse RB006 immediately after PCI. All PCI procedures were successful without angiographic procedural thrombotic events or catheter thrombus, and bleeding was infrequent. Baseline plasma and whole-blood activated partial thromboplastin time increased by 2.5- and 1.8-fold 5 minutes after RB006 and remained stable. Activated clotting time was ≥225 seconds in all cases and remained stable with RB006 but trended upward with unfractionated heparin. Partial RB007 reversal reduced RB006 activity by 51±14% to 68±15%. Complete reversal reduced RB006 activity by 93±11% to 103±13%, depending on the assay. Anticoagulation through factor IXa inhibition with RB006, followed by active reversal with RB007, was feasible and may favorably shift the balance of safety and efficacy during PCI. See p 614.
Differences Between Out-of-Hospital Cardiac Arrest in Residential and Public Locations and Implications for Public-Access Defibrillation
Whereas a tremendous amount of resources has focused on deployment of automated external defibrillators (AEDs) in public locations, the majority of out-of-hospital cardiac arrests (OHCAs) take place in residential areas and remain not covered by publicly placed AEDs. Furthermore, little is known about how to identify residential areas with the highest risk of OHCA, let alone the possible cost of public-access defibrillation in such areas. We therefore performed a systematic analysis of OHCAs in residential areas of Copenhagen to examine whether high-risk areas of OHCA suitable for AED placement could be identified. Using simple demographic characteristics of a city center, we were able to identify residential areas characterized by having at least 1 OHCA every 4.3 to 5.6 years within a 100×100-m area. These areas comprised <3% of all residential quarters but included up to 9% of all residential arrests. The estimated cost of AED deployment in selected residential areas was below $100 000 per quality-adjusted life-year but likely to exceed the corresponding cost for AED deployment in public locations. Furthermore, individuals with OHCAs in residential locations were more likely to have characteristics associated with a poor outcome compared with public ones in that the patients were older and more often male, the ambulance response interval was longer, arrests occurred more often at night, and the patients had ventricular fibrillation less often. Therefore, if future public-access defibrillation programs in residential areas are to succeed without excessive costs, strategic placement of AEDs in selected residential areas is a necessity. See p 623.
- Hypertension in Pregnancy and Later Cardiovascular Risk: Common Antecedents?
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