- Maximizing Survival Benefit With Primary Prevention Implantable Cardioverter-Defibrillator Therapy in a Heart Failure Population
- Prospective, Comprehensive Assessment of Cardiac Troponin T Testing After Coronary Artery Bypass Graft Surgery
- Influence of Renal Function on the Effects of Early Revascularization in Non–ST-Elevation Myocardial Infarction: Data From the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART)
- Age, Increased Left Ventricular Mass, and Lower Regional Myocardial Perfusion Are Related to Greater Extent of Myocardial Dyssynchrony in Asymptomatic Individuals: The Multi-Ethnic Study of Atherosclerosis
- Noninvasive Coronary Angiography by 320-Row Computed Tomography With Lower Radiation Exposure and Maintained Diagnostic Accuracy: Comparison of Results With Cardiac Catheterization in a Head-to-Head Pilot Investigation
- Cardiac Progenitor Cells and Biotinylated Insulin-Like Growth Factor-1 Nanofibers Improve Endogenous and Exogenous Myocardial Regeneration After Infarction
- Hydrogen Sulfide Improves Survival After Cardiac Arrest and Cardiopulmonary Resuscitation via a Nitric Oxide Synthase 3–Dependent Mechanism in Mice
- Nitrite Therapy After Cardiac Arrest Reduces Reactive Oxygen Species Generation, Improves Cardiac and Neurological Function, and Enhances Survival via Reversible Inhibition of Mitochondrial Complex I
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Maximizing Survival Benefit With Primary Prevention Implantable Cardioverter-Defibrillator Therapy in a Heart Failure Population
This analysis developed and validated a multivariate risk model (Seattle Heart Failure Model–D) in ≈10 000 heart failure patients. We prospectively applied the model to the Sudden Cardiac Death Heart Failure Trial to determine whether the benefit of a primary prevention implantable cardioverter-defibrillator (ICD) varies with the estimated annual mortality. The percentage of sudden death was inversely proportional to estimated annual mortality (low risk had a higher proportion of sudden death). The ICD benefit was greatest (≈90% reduction in sudden death and ≈50% reduction in all-cause mortality) in the lowest-risk patients who had an estimated annual mortality of ≈3% to 5%. In the highest-risk patients (≈20% annual mortality), the ICD was only ≈25% effective in reducing sudden death and had benefit in reducing total mortality. The years needed to treat 1 patient to add 1 year of life was 3.5 to 4.6 in 80% of patients but was 21.5 in the highest-risk patients (≈20% annual mortality). Each ICD adds 1.5 to 2 years of life in patients with an annual mortality of <15%. Use of a validated multivariate risk model may allow healthcare providers to better select patients for primary prevention ICDs and to describe the potential ICD benefit to patients in easily understood terminology. See p 835.
Prospective, Comprehensive Assessment of Cardiac Troponin T Testing After Coronary Artery Bypass Graft Surgery
The role of serum troponin measurement is well defined in the diagnosis and risk stratification of acute coronary syndromes. However, the situation is less clear for the use of troponin measurement after cardiac surgery because troponin is released in essentially all such patients. Therefore, we undertook a prospective study of 847 patients to comprehensively evaluate and validate the use of troponin T testing for risk assessment in this setting. In addition, we studied patients within the context of recent consensus guidelines for the detection of post–coronary artery bypass grafting (CABG) myocardial infarction. Only 2% of subjects had a post-CABG myocardial infarction; however, we found that troponin T concentrations were elevated in essentially all patients and were determined by several relevant preoperative, intraoperative, and postoperative factors. Importantly, very elevated troponin T concentrations were correlated with more resource use and poorer outcomes and were additive to the Society for Thoracic Surgery risk score for prognostication after CABG. Whereas the consensus-endorsed cut point for troponin T (0.15 ng/mL) was overly sensitive and less clinically useful for either post-CABG diagnosis of myocardial infarction or risk assessment, a higher troponin T of <1.60 ng/mL provided excellent negative predictive value for excluding relevant complications in post-CABG setting. Troponin testing after CABG is therefore valuable for postoperative risk assessment, particularly when applied at the correct cut points. See p 843.
Influence of Renal Function on the Effects of Early Revascularization in Non–ST-Elevation Myocardial Infarction: Data From the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART)
Renal dysfunction affects approximately 25% to 30% of patients admitted with an acute coronary syndrome. Its presence is associated with an exponential increase in mortality. Data to support current guidelines for early revascularization in patients with renal dysfunction admitted with a non–ST-elevation myocardial infarction are sparse, because clinical trials have often used elevated creatinine as an exclusion criterion. In this current nationwide registry from Sweden that included 23 262 patients between 2003 and 2006 who were 80 years old or younger, we evaluated whether early revascularization (by either percutaneous coronary intervention or coronary artery bypass grafting) within 14 days of admission for a non–ST-elevation myocardial infarction alters prognosis at all degrees of renal dysfunction. We found that patients with mild-to-moderate renal insufficiency had comparable survival benefit at 1 year with early revascularization. Despite this advantage with treatment, there was a lower use of an early invasive therapy in those with moderate renal insufficiency, among whom only 36% were revascularized compared with 62% of those with normal renal function. More frequent use of an invasive approach in those with mild-to-moderate renal dysfunction could potentially alter their worse outcome. In contrast, the advantage with revascularization in those with more advanced renal impairment is lower and less certain, and its use is questionable in those with renal failure or on dialysis, in whom there was a suggestion of harm with therapy. Further research to find the optimal therapy to improve prognosis for this patient group is needed. See p 851.
Age, Increased Left Ventricular Mass, and Lower Regional Myocardial Perfusion Are Related to Greater Extent of Myocardial Dyssynchrony in Asymptomatic Individuals: The Multi-Ethnic Study of Atherosclerosis
Age and myocardial hypertrophy are associated with the development of left ventricular (LV) dysfunction and heart failure. Myocardial dyssynchrony is also related to the development and progression of heart failure. Our goal was to study the relationship of LV mass and age with dyssynchrony in asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis and to obtain more insight into the mechanisms underlying the development of myocardial dysfunction. A total of 1100 individuals underwent tagged magnetic resonance imaging. Their regional LV function was analyzed with the use of time parameters of myocardial deformation including time to peak systolic strain and strain rate. Myocardial dyssynchrony was expressed by SD of time to peak strain and strain rate. There was a direct relationship between age and delayed time to peak strain and a greater extent of dyssynchrony. Importantly, there was also significant association between LV mass and time to peak strain, time to peak strain rate, and the SD of time to strain rate. In a subset of patients (n=74), the relationship between myocardial perfusion and timing of contraction was studied. Decreased myocardial perfusion at rest was associated with delayed contraction and increased extent of dyssynchrony. These new data may enhance our understanding of the development of myocardial dysfunction and its possible prevention. We believe that myocardial dyssynchrony may explain, at least partly, the well-known association between aging and LV hypertrophy and LV dysfunction. This association may be mediated by changes in myocardial perfusion. However, the temporal relationships between aging, LV hypertrophy, reduced myocardial perfusion, dyssynchrony, and LV dysfunction should be clarified further. See p 859.
Noninvasive Coronary Angiography by 320-Row Computed Tomography With Lower Radiation Exposure and Maintained Diagnostic Accuracy: Comparison of Results With Cardiac Catheterization in a Head-to-Head Pilot Investigation
Our head-to-head comparison of whole-heart 320-row computed tomography (CT) and conventional coronary angiography has important clinical implications because it shows that 320-row coronary CT angiography has high diagnostic accuracy for detection of coronary artery stenoses, whereas radiation exposure (determined as “effective dose in mSv”) is significantly lower (4.2 versus 8.5 mSv) than that of conventional coronary angiography. Because noninvasive coronary CT angiography would be best applied as a rule-out test to all persons with low to intermediate pretest likelihood of coronary artery disease to avoid unnecessary conventional coronary angiography and thereby reduce complications and risks, it is of tremendous importance to reduce the previously high burden of ionizing radiation of coronary CT angiography. Using whole-heart data prospectively acquired with 320-row CT greatly reduces exposure because it avoids radiation-intensive overscanning and overranging. Moreover, it also increases image quality and results in good diagnostic performance because data are typically acquired in a fraction of a second (0.45 to 0.6 second) during a single heartbeat (if heart rate is <65 bpm). Thus, the entire 3-dimensional data set is temporally uniform and not constructed from multiple consecutive heartbeats as with scanners not covering the entire heart in a snapshot (because of fewer detector rows), thereby reducing heart rate– and breathing-related motion artifacts. Finally, this whole-heart approach has the long-term clinical potential to develop 4-dimensional acquisition strategies for additional analysis of myocardial perfusion with the use of 320-row CT. Such an approach might enable comprehensive evaluation of a range of patients with known or suspected coronary artery disease. See p 867.
Cardiac Progenitor Cells and Biotinylated Insulin-Like Growth Factor-1 Nanofibers Improve Endogenous and Exogenous Myocardial Regeneration After Infarction
Myocardial infarction is characterized by an extensive loss of cardiomyocytes and vascular structures, and the size of the initial insult is a critical determinant of the evolution of the postinfarcted heart and negative ventricular remodeling. Resident cardiac progenitor cells (CPCs) do not migrate spontaneously to the area of damage, and healing is associated with scar formation and alterations in cardiac structure and function. Recent clinical trials have suggested that the intracoronary delivery or intramyocardial injection of adult autologous progenitor cells may have a beneficial effect on the treatment of acute and chronic heart failure in patients. At least 3 possibilities have been advanced: (1) myocardial regeneration mediated by differentiation of the delivered cells; (2) paracrine effects triggered by activation of resident progenitor cells; and (3) a combination of both processes. In the present study, we tested whether the local administration of CPCs together with insulin-like growth factor-1 tethered to self-assembling peptide nanofibers enhanced the activation and differentiation of exogenous and endogenous CPCs potentiating cardiac repair after infarction. By this strategy, the growth and differentiation of the delivered CPCs were markedly increased, and these positive aspects of myocardial regeneration were accompanied by intense recruitment of resident CPCs. This pool of tissue-specific progenitor cells rapidly acquired the adult cardiomyocyte phenotype. In comparison with infarcts treated with CPCs alone, combination therapy resulted in a greater recovery of myocardial structure and ventricular performance. Collectively, our observations point to the potential therapeutic import of CPCs and nanofibers engineered to deliver growth factors for the management of ischemic cardiomyopathy in humans. See p 876.
Hydrogen Sulfide Improves Survival After Cardiac Arrest and Cardiopulmonary Resuscitation via a Nitric Oxide Synthase 3–Dependent Mechanism in Mice
Sudden cardiac arrest is one of the leading causes of death worldwide. Despite advances in cardiopulmonary resuscitation (CPR) methods, including the introduction of the automatic electric defibrillator and therapeutic hypothermia, 60% to 80% of these arrests result in immediate death, and of the remaining, only ≈5% are successfully resuscitated to the extent that they are returned to productive lives. Poor outcome from cardiac arrest is at least partly due to the lack of therapeutic possibilities. In this study, we examined effects of hydrogen sulfide, a gaseous molecule with multifaceted protective properties, on the outcome of cardiac arrest and CPR in mice. We found that administration of sodium sulfide, a hydrogen sulfide donor, 1 minute before CPR markedly improved neurological and myocardial function and survival after 8 minutes of cardiac arrest in mice. These observations, if extrapolated to human beings, may be highly clinically relevant because they suggest that sodium sulfide administration can improve the outcome of sudden cardiac arrest at the time of CPR when intravenous access is obtained. Further studies are warranted to elucidate the impact of exogenous and endogenous hydrogen sulfide on the longer-term outcome of cardiac arrest and CPR complicated by post–cardiac arrest syndrome. See p 888.
Nitrite Therapy After Cardiac Arrest Reduces Reactive Oxygen Species Generation, Improves Cardiac and Neurological Function, and Enhances Survival via Reversible Inhibition of Mitochondrial Complex I
Cardiac arrest results in significant morbidity and mortality driven mainly by the cardiac and neurological injury resulting from global ischemia and reperfusion injury. Although resuscitation rates can exceed 65% for some rhythms, between 50% and 75% of these patients die before hospital discharge, and up to a third of survivors suffer significant brain injury. Only hypothermia has shown clinical benefit as a postresuscitation therapy in a subset of patients. Clearly, additional therapies are needed. The recent finding that nitrite acts as an ischemic reservoir for enzyme-independent nitric oxide generation has resulted in numerous animal studies in which it has been proven beneficial in reducing focal ischemic organ injury. On the basis of promising results in focal heart and brain ischemia, we have adapted a mouse model of cardiac arrest to model the high clinical mortality and myocardial and neurological dysfunction associated with cardiac arrest. In this model, nitrite therapy given at the start of resuscitation resulted in significant improvements in survival and myocardial and neurological function in survivors. We further investigate the potential mechanism for cardioprotection that involves the role of nitrite as a mitochondrial antioxidant early in resuscitation. The significant benefits attributed to nitrite, along with its ease of delivery and known primate and human safety data, make this a promising therapy for a condition with few current therapeutic options. See p 897.
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