Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Ten-Year Incidence of Chagas Cardiomyopathy Among Asymptomatic Trypanosoma cruzi–Seropositive Former Blood Donors
- H2S Protects Against Pressure Overload–Induced Heart Failure via Upregulation of Endothelial Nitric Oxide Synthase
- Imatinib Mesylate as Add-on Therapy for Pulmonary Arterial Hypertension: Results of the Randomized IMPRES Study
- “Picture to Puncture”: A Novel Time Metric to Enhance Outcomes in Patients Transferred for Endovascular Reperfusion in Acute Ischemic Stroke
- Prognostic Value of Energy Loss Index in Asymptomatic Aortic Stenosis
- Info & Metrics
Ten-Year Incidence of Chagas Cardiomyopathy Among Asymptomatic Trypanosoma cruzi–Seropositive Former Blood Donors
This study presents the results from a large, retrospective cohort study of Chagas cardiomyopathy incidence from a National Heart, Lung, and Blood Institute–funded multicenter study in Brazil. After an average follow-up of 11 years, cohorts of previously healthy Trypanosoma cruzi–seropositive and –seronegative blood donors were subjected to comprehensive cardiology evaluations. We estimated a cardiomyopathy incidence of 1.85 per 100 person-years attributable to T cruzi infection. These results are important on several levels. First, in terms of knowledge about the pathogenesis of Chagas disease, we present well-controlled data on cardiomyopathy incidence among previously asymptomatic T cruzi seropositives. Previous studies have relied on case series derived from referral centers, so our incidence estimates better represent those of seropositives in the general population. Second, the inclusion of T cruzi seronegatives as control subjects allowed us to validate our screening diagnostic algorithm by estimating the fraction of cardiomyopathy cases resulting from other causes that may be erroneously attributed to Chagas disease. This is important in that endemic countries in Latin America attain living standards that bring with them an increasing incidence of atherosclerotic cardiovascular disease. Third, the data will allow public health authorities to better estimate the potential disease burden and to calculate the costs and benefits of antitrypanosomal treatment in asymptomatic seropositives. Finally, these data will be of interest to the practicing cardiologist in the United States who may increasingly encounter T cruzi–seropositive patients among immigrants from Latin America. They will allow her/him to better estimate prognosis and to better consider treatment. See p 1105.
H2S Protects Against Pressure Overload–Induced Heart Failure via Upregulation of Endothelial Nitric Oxide Synthase
Despite decades of research, heart failure continues to be a major health problem, as evidenced by a rise in the number of hospitalizations for heart failure, the number of deaths attributed to heart failure, and the ever-increasing costs associated with its care. Hydrogen sulfide (H2S) is a recently identified, endogenous, gaseous signaling molecule that modulates diverse physiological signals and protects the myocardium during ischemia/reperfusion. Recent clinical evidence suggests that circulating H2S levels are decreased in patients with heart failure and that the severity of heart failure is inversely correlated with H2S bioavailability. In the present study, we examined the effects of H2S deficiency and H2S therapy on the severity of cardiac hypertrophy and heart failure in mice after transverse aortic banding. Mice deficient in a key H2S-generating enzyme exhibited exacerbated heart failure, whereas mice with cardiac-restricted overexpression of this enzyme were protected against heart failure. We also demonstrated that a novel H2S donor significantly attenuates adverse left ventricular modeling and preserves left ventricular function when administered before the onset of heart failure. Key actions of H2S involved reductions in oxidative stress and myocardial fibrosis, coupled with increased myocardial capillary density. Additional experiments determined that the cardioprotective effects of H2S therapy were mediated via upregulation of endothelial nitric oxide synthase and increased nitric oxide bioavailability. Together, these findings further support the emerging concept that H2S therapy may be of clinical importance in the treatment of cardiovascular disease and may have a practical clinical use. See p 1116.
Imatinib Mesylate as Add-on Therapy for Pulmonary Arterial Hypertension: Results of the Randomized IMPRES Study
Pulmonary arterial hypertension (PAH) is a progressive and frequently fatal condition. Platelet-derived growth factor and c-KIT signaling are important in vascular smooth muscle cell proliferation and hyperplasia, which are cardinal features of the pathophysiology underlying the disease. Imatinib is an inhibitor of platelet-derived growth factor receptor α and β kinases and c-KIT and may have a role in the treatment of PAH. The Imatinib in Pulmonary Arterial Hypertension, a Randomized, Efficacy Study (IMPRES) was a double-blind, placebo-controlled, randomized, 24-week trial evaluating the efficacy and safety of imatinib in PAH patients with high pulmonary vascular resistance (≥800 dyne·s·cm−5) receiving ≥2 PAH therapies (endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and/or prostacyclin analogues). Compared with placebo, imatinib significantly improved exercise capacity and hemodynamic parameters in patients with advanced PAH who remained symptomatic on at least 2 of the currently available drug classes. Discontinuations of study medication and serious adverse events, including subdural hematoma, were more common in the imatinib group. The results suggest that the efficacy profile of imatinib is promising for the treatment of PAH patients who are still symptomatic despite receiving ≥2 PAH therapies, although clinicians should take note of its safety profile, which continues to be assessed in ongoing studies. See p 1128.
“Picture to Puncture”: A Novel Time Metric to Enhance Outcomes in Patients Transferred for Endovascular Reperfusion in Acute Ischemic Stroke
The evolution of time metrics in the field of percutaneous coronary angioplasty has been the cornerstone for much of the past decade in the establishment of institutional guidelines and expectations for the treatment of patients with ST-segment elevation myocardial infarctions. From the introduction of “door-to-balloon” to the development of “door-in door-out” times, interventional cardiology has transformed the way in which we capture system processes and maintain standards of care for our patients. The field of neurointerventional surgery, however, has been slower to develop time metrics and expectations of system processes for intra-arterial therapies for stroke. Increasing numbers of trials surrounding endovascular reperfusion therapy along with the development of regional stroke centers will bring the issue of efficient systems to the forefront. We are concerned that clinical trials may continue to fail to show the benefit of endovascular reperfusion treatment because system processes have not been optimized, particularly surrounding interfacility transfers. In this article, we present a novel metric, “picture-to-puncture,” that captures the continuum of care from initial computed tomography to groin puncture and is associated with patient outcomes after endovascular reperfusion for ischemic strokes. This novel metric will allow for universal comparison of institutional practices and promote new ways of streamlining interfacility transfers among this patient population. We believe that this timely report will bring attention to a crucial topic surrounding endovascular treatments for stroke and will help to encourage further efficiencies in endovascular stroke therapies in the future. See p 1139.
Prognostic Value of Energy Loss Index in Asymptomatic Aortic Stenosis
Aortic stenosis (AS) severity is frequently overestimated by aortic valve area based on the continuity equation in patients with milder degree of AS or smaller aortic root dimensions. Conventional measures of AS severity such as peak jet velocity, mean aortic gradient, and aortic valve area may also grade AS inconsistently. From this, we hypothesized that adjusting aortic valve area for the pressure recovery occurring in the aortic root by calculating the energy loss index (ELI) would improve risk assessment in patients with asymptomatic mild to moderate AS. This was tested in a prospective study of 1563 patients with initially asymptomatic AS and without known atherosclerotic disease or diabetes mellitus. In Cox regression analysis, lower ELI predicted higher risk for aortic valve events, including aortic valve replacement, cardiovascular death, and heart failure resulting from progression of AS, and higher mortality and combined total mortality and hospitalization for heart failure caused by progression of AS independently of peak aortic jet velocity and mean aortic gradient. To test whether ELI was superior to mean aortic gradient in event prediction, reclassification analysis was performed. As demonstrated, ELI improved aortic valve event prediction in the total study population, whereas prediction of total mortality and hospitalization for heart failure caused by progression of AS was improved only in the subgroup of patients with an aortic diameter <2.6 cm at the sinotubular junction. The results of the present study support systematic calculation of ELI in asymptomatic AS patients. ELI may be particularly useful in AS patients with a small aortic root. See p 1149.
- © 2013 American Heart Association, Inc.
- Prognostic Value of Energy Loss Index in Asymptomatic Aortic Stenosis
- Info & Metrics