Current Smoking and Prognosis After Acute ST-Segment Elevation Myocardial Infarction: New Pathophysiological Insights.

OBJECTIVES: The aim of this study was to mechanistically investigate associations among cigarette smoking, microvascular pathology, and longer term health outcomes in patients with acute ST-segment elevation myocardial infarction (MI). BACKGROUND: The pathophysiology of myocardial reperfusion injury and prognosis in smokers with acute ST-segment elevation MI is incompletely understood. METHODS: Patients were prospectively enrolled during emergency percutaneous coronary intervention. Microvascular function in the culprit artery was measured invasively. Contrast-enhanced magnetic resonance imaging (1.5-T) was performed 2 days and 6 months post-MI. Infarct size and microvascular obstruction were assessed using late gadolinium enhancement imaging. Myocardial hemorrhage was assessed with T2* mapping. Pre-specified endpoints included: 1) all-cause death or first heart failure hospitalization; and 2) cardiac death, nonfatal MI, or urgent coronary revascularization (major adverse cardiovascular events). Binary logistic regression (odds ratio [OR] with 95% confidence interval [CI]) with smoking status was used. RESULTS: In total, 324 patients with ST-segment elevation MI were enrolled (mean age 59 years, 73% men, 60% current smokers). Current smokers were younger (age 55 ± 11 years vs. 65 ± 10 years, p < 0.001), with fewer patients with hypertension (52 ± 27% vs. 53 ± 41%, p = 0.007). Smokers had better TIMI (Thrombolysis In Myocardial Infarction) flow grade (≥2 vs. ≤1, p = 0.024) and ST-segment resolution (none vs. partial vs. complete, p = 0.010) post-percutaneous coronary intervention. On day 1, smokers had higher circulating C-reactive protein, neutrophil, and monocyte levels. Two days post-MI, smoking independently predicted infarct zone hemorrhage (OR: 2.76; 95% CI: 1.42 to 5.37; p = 0.003). After a median follow-up period of 4 years, smoking independently predicted all-cause death or heart failure events (OR: 2.20; 95% CI: 1.07 to 4.54) and major adverse cardiovascular events (OR: 2.79; 95% CI: 2.30 to 5.99). CONCLUSIONS: Smoking is associated with enhanced inflammation acutely, infarct-zone hemorrhage subsequently, and longer term adverse cardiac outcomes. Inflammation and irreversible myocardial hemorrhage post-MI represent mechanistic drivers for adverse long-term prognosis in smokers. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction. [BHF MR-MI]; NCT02072850).

Quantification of infarct size and myocardium at risk: evaluation of different techniques and its implications.

AIMS: The aim of this study was to evaluate seven methods for quantifying myocardial oedema [2 standard deviation (SD), 3 SD, 5 SD, full width at half maximum (FWHM), Otsu method, manual thresholding, and manual contouring] from T2-weighted short tau inversion recovery (T2w STIR) and also to reassess these same seven methods for quantifying acute infarct size following ST-segment myocardial infarction (STEMI). This study focuses on test-retest repeatability while assessing inter- and intraobserver variability. T2w STIR and late gadolinium enhancement (LGE) are the most widely used cardiovascular magnetic resonance (CMR) techniques to image oedema and infarction, respectively. However, no consensus exists on the best quantification method to be used to analyse these images. This has potential important implications in the research setting where both myocardial oedema and infarct size are increasingly used and measured as surrogate endpoints in clinical trials. METHODS AND RESULTS: Forty patients day 2 following acute reperfused STEMI were scanned for myocardial oedema and infarction (LGE). All patients had a second CMR scan on the same day >6 h apart from the first one. Images were analysed offline by two independent observers using the semi-automated software. Both oedema and LGE were quantified using seven techniques (2 SD, 3 SD, 5 SD, Otsu, FWHM, manual threshold, and manual contouring). Interobserver, intraobserver and test-retest agreement and variability for both infarct size and oedema quantification were assessed. Infarct size and myocardial quantification vary depending on the quantification method used. Overall, manual contouring provided the lowest inter-, intraobserver, and interscan variability for both infarct size and oedema quantification. The FWHM method for infarct size quantification and the Otsu method for myocardial oedema quantification are acceptable alternatives. CONCLUSIONS: This study determines that, in acute myocardial infarction (MI), manual contouring has the lowest overall variability for quantification of both myocardial oedema and MI when analysed by experienced observers.

Morphological changes associated with hemodynamically significant myocardial bridges in sudden cardiac death.

UNLABELLED: Although myocardial bridging (MB) is a common coronary anomaly, its cardiovascular consequences are still disputed. A positive link between sudden cardiac death (SCD) and myocardial bridging has not yet been definitively proved, even though many case reports and small scale studies support this association. For myocardial bridging to be associated with sudden cardiac death it must exhibit certain specific characteristics involving coronary or myocardial changes sufficient to explain a terminal cardiac event. In this study we aimed to analyze the morphological changes (both myocardial and coronary) associated with hemodynamically significant myocardial bridging and the morphological differences between hemodynamically significant MB and MB considered to be non-hemodynamically significant. MATERIAL AND METHOD: We analyzed 53 cases of sudden cardiac death, of which 21 cases had hemodynamically significant myocardial bridging, 14 had non-hemodynamically significant myocardial bridging and 20 cases suffered sudden cardiac death without myocardial bridging, using a morphological score with seven histological parameters. RESULTS: Myocardial fibrosis and interstitial edema were found to be highly correlated with hemodynamically significant myocardial bridging (HSMB), as were interstitial edema and interstitial fibrosis. CONCLUSIONS: Hemodynamically significant myocardial bridging can be discovered during heart dissection by analyzing a series of morphological markers (width, distribution of atherosclerosis, distal hypoplasia). Our study showed that MB was associated with increased myocardial fibrosis and edema, both of which have an increased risk of electrical instability. Compared to non-hemodynamically significant myocardial bridging, HSMB shows a distinct histological pattern, with increased myocardial fibrosis and edema. The main cause of SCD in association with HSMB seems to be electrical due to increased electrical myocardial heterogeneity, but large scale studies are needed to test this.

Mortality in acute cardiogenic pulmonary edema treated with continuous positive airway pressure.

OBJECTIVE: To investigate mortality in acute cardiogenic pulmonary edema (ACPE) patients treated with continuous positive airway pressure (CPAP) and to identify clinical and laboratory characteristics associated with mortality. DESIGN: Observational, retrospective study. SETTING: Emergency Medicine Department. PATIENTS AND PARTICIPANTS: A total of 454 consecutive ACPE patients treated with CPAP. MEASUREMENTS AND RESULTS: Demographics, past medical history, clinical characteristics, laboratory evaluation, in-hospital mortality data were collected. Potential predictors of in-hospital mortality that were considered of clinical relevance and immediately accessible on admission were investigated by multivariable logistic regression. ACPE-related mortality rate was 3.8% (17/452 patients) and the in-hospital mortality rate was 11.4% (50/440 patients). Significant independent predictors of increased risk of in-hospital mortality were: advanced age (P = 0.012), normal-to-low blood pressure (P < 0.001), low PaO(2)/FiO(2) ratio (P = 0.020), hypocapnia (P = 0.009) and anemia (P = 0.05). CONCLUSIONS: Values recorded within few minutes from arrival to the hospital can predict mortality in ACPE patients treated with CPAP who has been tested, for the first time, in a real life study. This can allow physicians to quickly recognize more severe ACPE patients treated with CPAP and plan for aggressive monitoring and treatment and for deciding the better site of care.

A randomized, controlled trial of the renal effects of ultrafiltration as compared to furosemide in patients with acute decompensated heart failure.

OBJECTIVES: This study was designed to evaluate the consequences of ultrafiltration (UF) and standard intravenous diuretic (furosemide) therapy on glomerular filtration rate (GFR) and renal plasma flow in patients with acute decompensated heart failure. BACKGROUND: It has been hypothesized that treatment with diuretics may worsen renal function as the result of systemic neurohormonal activation and direct renal vascular effects. UF also removes fluid, but its actions on intrarenal hemodynamics, and therefore renal function, are unknown. METHODS: Patients hospitalized for acute decompensated heart failure with an ejection fraction less than 40% and two or more signs of hypervolemia were randomized to receive UF or intravenous diuretics. Urine output, GFR (as measured by iothalamate), and renal plasma flow (as measured by para-aminohippurate) were assessed before fluid removal and after 48 hours. RESULTS: Nineteen patients (59 +/- 16 years, 68% were male) were randomized to receive UF (n = 9) or intravenous diuretics (n = 10). The change in GFR (-3.4 +/- 7.7 mL/min vs. -3.6 +/- 11.5 mL/min; P = .966), renal plasma flow (26.6 +/- 62.7 mL/min vs. 16.1 +/- 42.0 mL/min; P = .669), and filtration fraction (-6.9 +/- 13.6 mL/min vs. -3.9 +/- 13.6 mL/min; P = .644) after treatment were not significantly different between the UF and furosemide treatment groups, respectively. There was no significant difference in net 48-hour fluid removal between the groups (-3211 +/- 2345 mL for UF and -2725 +/- 2330 mL for furosemide, P = .682). UF removed 3666 +/- 2402 mL. Urine output during 48 hours was significantly greater in the furosemide group (5786 +/- 2587 mL) compared with the UF group (2286 +/- 915 mL, P < .001). CONCLUSIONS: During a 48-hour period, UF did not cause any significant differences in renal hemodynamics compared with the standard treatment of intravenous diuretics.

The pathophysiology of acute heart failure--is it all about fluid accumulation?

Despite significant advancement in chronic heart failure (HF), no breakthroughs have occurred in the last 2 decades in our understanding of the pathophysiology, classification, and treatment of acute HF (AHF). Traditional thinking, which has been that this disorder is a result of gradual fluid accumulation on a background of chronic HF, has been called into question by recent large registries enrolling less selected patient populations. It is increasingly recognized that many patients with this syndrome are elderly, have relatively preserved ejection fraction, and have mild or no preexisting chronic HF. In this review, we propose 2 primary subtypes of AHF: (1) acute decompensated cardiac failure, characterized by deterioration of cardiac performance over days to weeks leading to decompensation; and (2) acute vascular failure, characterized by acute hypertension and increased vascular stiffness. Registry data suggest that the latter is the more common form of AHF in the general population, although the former is often overrepresented in studies focused in academic tertiary care centers. Regardless of the clinical subtype, a variety of pathophysiologic mechanisms may play a role in this disorder, many of which remain poorly understood. In this review, we describe current understanding of the pathophysiology of AHF, including a critical evaluation of the data supporting both traditional and novel mechanisms, and suggest a framework for integrating these mechanisms into an overall model of AHF.