Cinzia Zuchi

The 'Echo Heart Failure Score': an echocardiographic risk prediction score of mortality in systolic heart failure.

Although many transthoracic echocardiographic (TTE) measurements have been shown to predict outcome in heart failure (HF), whether incremental risk prediction is afforded by their combination is unknown. We developed a simple echocardiographic risk score of mortality in HF patients.

Presence of extensive LV remodeling limits the benefits of CRT in patients with intraventricular dyssynchrony.

OBJECTIVES The aim of this study was to evaluate whether, in patients with evidence of both electrical and mechanical left ventricular (LV) dyssynchrony, extensive LV dilation would affect response to cardiac resynchronization therapy (CRT). BACKGROUND Cardiac resynchronization therapy is effective in heart failure patients with LV dysfunction and wide QRS complex. However, many patients still fail to respond. We hypothesized that presence of extensive LV dilation might prevent response to CRT, despite LV mechanical dyssynchrony. METHODS We studied 78 heart failure patients (68 ± 9 years of age, 77% men) with both electrical (QRS width >120 ms) and mechanical intraventricular dyssynchrony (by tissue Doppler imaging and/or left lateral wall post-systolic contraction). Echocardiographic evaluation was performed at baseline and 6 to 8 months after CRT. As an indication of LV remodeling, end-diastolic volume index and end-systolic volume index (ESVI) and sphericity index were measured. Long-term (40 ± 23 months) clinical follow-up (events: cardiac death and hospital admission for heart failure) was also obtained. RESULTS At follow-up after CRT, in the overall population, ejection fraction increased from 26 ± 6% to 35 ± 11% (p < 0.0001), whereas end-diastolic volume index (from 144 ± 43 ml/m(2) to 119 ± 55 ml/m(2)), ESVI (from 108 ± 37 ml/m(2) to 82 ± 49 ml/m(2), p < 0.0001 for both), and sphericity index (from 0.60 ± 0.22 to 0.53 ± 0.15, p = 0.0036) all significantly decreased. By multiple linear regression analysis, after controlling for confounding factors, change in LV ejection fraction at follow-up resulted independently and negatively associated with baseline ESVI (p = 0.001), with much lower improvement after implant in the highest tertile of baseline ESVI. During follow-up, 31 patients (39.7%) had a cardiac event. By Cox regression model, baseline ESVI was the most powerful predictor of events, with event-rate/year increasing with increasing tertiles of ESVI (6.3%, 10.1%, and 23.8%, respectively, p < 0.05). CONCLUSIONS In this nonrandomized, open-label clinical study, despite intraventricular electrical and mechanical dyssynchrony, extensive LV remodeling at baseline negatively impacted CRT results in terms of LV function improvement and incidence of cardiac events at follow-up.

Impact of chronic antiplatelet therapy before hospitalization on ischemic and bleeding events in invasively managed patients with acute coronary syndromes: the ACUITY trial.

Aims: Presentation with an acute coronary syndrome (ACS) on chronic aspirin therapy is an independent predictor of adverse short-term outcomes. Whether this finding applies to chronic thienopyridine use, and with the contemporary invasive management of ACS, is unknown. Methods and results: In ACUITY, 13819 patients with moderate and high-risk ACS were studied; patients transferred from an outside hospital were excluded from the present analysis, given uncertain preadmission antiplatelet status. Endpoints included major adverse cardiovascular events (MACE: death, myocardial infarction, or unplanned revascularization), major bleeding, and net adverse clinical events (NACE). Among 11313 study patients, 31 % were naive for antiplatelet agent, 49% were receiving aspirin alone, and 20% were on dual antiplatelet therapy. Chronic antiplatelet users were older and had a higher risk profile. After adjusting for baseline differences, chronic antiplatelet therapy (single or dual) was not associated with an increased incidence of 30-day MACE, bleeding, or NACE. However, patients on chronic aspirin or dual antiplatelet therapy at presentation had significantly higher 1-year rates of MACE [odds ratio (95% confidence interval) = 1.17 (1.01–1.36), P = 0.03 and 1.29 (1.02–1.64), P = 0.03, respectively]. Patients presenting on dual antiplatelet therapy had significantly greater adjusted MACE at 1-year than those on aspirin alone [odds ratio (95% confidence interval) = 1.34 (1.15–1.56), P < 0.0001]. Conclusion: Contrary to earlier studies, prior antiplatelet therapy was not associated with an increased risk of adverse outcomes at 30 days in invasively managed patients. Such use did, however, independently predict 1-year ischemic MACE, with outcomes worse for patients presenting on chronic dual antiplatelet therapy compared with aspirin alone.

Prognostic Value of Right Ventricular Dysfunction in Heart Failure With Reduced Ejection Fraction: Superiority of Longitudinal Strain Over Tricuspid Annular Plane Systolic Excursion

Background— In heart failure (HF) with reduced ejection fraction, right ventricular (RV) impairment, as defined by reduced tricuspid annular plane systolic excursion, is a predictor of poor outcome. However, peak longitudinal strain of RV free wall (RVFWS) has been recently proposed as a more accurate and sensitive tool to evaluate RV function. Accordingly, we investigated whether RVFWS could help refine prognosis of patients with HF with reduced ejection fraction in whom tricuspid annular plane systolic excursion is still preserved. Methods and Results— A total of 200 patients with HF with reduced ejection fraction (age, 66±11 years; ejection fraction, 30±7%) with preserved tricuspid annular plane systolic excursion (>16 mm) underwent RV function assessment using speckle-tracking echocardiography to measure peak RVFWS. After a median follow-up period of 28 months, 62 (31%) patients reached the primary composite end point of all-cause death/HF rehospitalization. Median RVFWS was −19.3% (interquartile range, −23.3% to −15.0%). By lasso-penalized Cox-hazard model, RVFWS was an independent predictor of outcome, along with Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure-HF score, Echo-HF score, and severe mitral regurgitation. The best cutoff value of RVFWS for prediction of outcome was −15.3% (area under the curve, 0.68; P<0.001; sensitivity, 50%; specificity, 80%). In 50 patients (25%), RVFWS was impaired (ie, ≥−15.3%); event rate (per 100 patients per year) was greater in them than in patients with RVFWS <−15.3% (29.5% [95% confidence interval, 20.4–42.7] versus 9.4% [95% confidence interval, 6.7–13.1]; P<0.001). RVFWS yielded a significant net reclassification improvement (0.584 at 3 years; P<0.001), with 68% of nonevents correctly reclassified. Conclusions— In patients with HF with reduced ejection fraction with preserved tricuspid annular plane systolic excursion, RV free-wall strain provides incremental prognostic information and improved risk stratification.

Therapy Against Reperfusion-induced Microvascular Injury

No-reflow, i.e., the lack of distal myocardial perfusion to fully recover following recanalization of an acutely occluded coronary artery, is not only a mere consequence of ischemic injury, as substantial microvascular alterations may also develop subsequently, after initial restoration of perfusion. Since part of perfusion impairment is secondary to events set in motion by reperfusion, this gives way to the possibility of preventing it through adequate interventions. Duration and severity of ischemia influence the occurrence of reperfusion-mediated no-reflow, since severity of ischemic injury sets the stage for events which actually unfold after restoration of blood flow. Proposed mechanisms of no-reflow are impaired vasodilation, intravascular thrombosis, and accumulation of neutrophils in the microvasculature, orchestrated by activation of vascular endothelium. Experimental studies have unraveled much of mechanisms of noreflow, and delineated possible ways of intervention. Despite successful experimental data, in the clinical setting results have been much less encouraging, and no drug can be currently recommended for routine use to prevent or treat microvascular injury and no-reflow in patients. Reperfusion-mediated impairment of microcirculation in postischemic hearts remains a challenges for investigators and clinicians alike. Large multicenter studies, specifically aimed at evaluating the effects of the more promising interventions (adenosine, nicorandil, statins, ACE inhibitors or angiotensin II receptor blockers) need to be designed and performed, to test the effect of these promising interventions on microvascular alterations during postischemic reflow, and their ability to improve tissue perfusion, myocardial function and prognosis in patients with acute myocardial infarction.

Microvascular Angina in Different Clinical Conditions: Diabetes and the Metabolic Syndrome

Metabolic syndrome results in a pro-thrombotic, pro-inflammatory condition that markedly favours the development of diabetes and cardiovascular disease. In patients with metabolic syndrome, many interrelated factors are thought to contribute to the development of vascular alterations; however, insulin resistance is regarded as the most relevant. In fact, in addition to its well-known activity on glucose metabolism, insulin exerts a wide spectrum of non-metabolic actions, including vasodilation, inhibition of platelet aggregation and thrombosis, anti-oxidant and anti-inflammatory effects, which result in anti-atherosclerotic and vascular protective effects. In this setting, clustering of multiple cardiovascular risk factors may reinforce their pro-atherogenic potential. Metabolic syndrome is also accompanied by endothelial dysfunction, and it has become appreciated that microvascular damage is a common finding in these subjects. In diabetic patients, impairment of microcirculation is recognized at the level of all circulatory districts, including coronary microvessels, and it has an important prognostic impact. Diabetes is accompanied by profound changes in energy metabolism, increased oxidative stress, derangement of adipokines synthesis, reduced mobilization and function of endothelial progenitor cells, which may lead to microvascular dysfunction. Features of the insulin resistance syndrome, including altered glucose tolerance, are more frequent in patients with microvascular angina. Taken together, these observations suggest that diabetes, along with each of the various components of the metabolic syndrome, has the capability of profoundly altering coronary microvascular reactivity, thus predisposing to myocardial ischemia even in the absence of coronary artery stenosis. When these alterations combine in the same patient to give rise to full-blown metabolic syndrome, their negative effects on myocardial perfusion are synergistically potentiated. While the pathophysiology of this condition has become to be substantially unravelled, much research is still needed to achieve a tailored therapeutic approach.