Electrical remodeling reflected by QRS and T vector changes following cardiac resynchronization therapy is related to survival in heart failure patients with left bundle branch block.

INTRODUCTION: We investigated changes in electrocardiographic spatial QRS and T vectors as markers of electrical remodeling before and after cardiac resynchronization therapy (CRT) and their association with altered outcome. METHODS AND RESULTS: In 41 patients with LBBB, ECGpost was recorded during intrinsic rhythm after interrupting CRT pacing and compared to the pre-implant ECGpre and the ECG during CRT (ECGCRT). Mean spatial angles between QRS and T vectors were determined with the Kors matrix conversion. Left ventricular ejection fraction (LVEF) was determined with nuclear isotope ventriculography before CRT implantation (LVEFpre) and at inclusion (LVEFpost). Following CRT, LVEF improved significantly from 26 ± 10 to 36 ± 14% (p=0.01). Duration of QRSpre (168 ± 15 ms) was not different from QRSpost (166 ± 15 ms). A smaller angle between QRSCRT and Tpost was related to a greater angle between Tpre and Tpost (Pearson's R -0.61 - p<0.001). During follow-up (30 ± 2 months) 9 patients (22%) died. Univariate Cox regression revealed higher mortality in the patients with lower LVEFpost (HR 1.10, p=0.01), a larger angle QRSCRTTpost (HR 1.03, p=0.03), a smaller angle QRSpreQRSpost (HR 0.97, p=0.03) and smaller angle TpreTpost (HR 0.95, p<0.01). After adjusting for LVEFpost, only smaller angle TpreTpost was associated with mortality (HR 0.96, p=0.03). CONCLUSIONS: Electrical remodeling can be quantified by measuring the angles between spatial QRS and T vectors before, during and after CRT. In absence of QRS duration changes, more extensive electrical remodeling is associated with a significantly better survival. QRS and T vector changes deserve further investigation to better understand the individual response to CRT.

Heart failure with preserved ejection fraction or non-cardiac dyspnea in paroxysmal atrial fibrillation: The role of left atrial strain.

BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea and paroxysmal atrial fibrillation (AF) is challenging. Speckle tracking-derived left atrial strain (LAS) provides an accurate estimate of left ventricular (LV) filling pressures and left atrial (LA) phasic function. However, data on clinical utility of LAS in patients with dyspnea and AF are scarce. OBJECTIVE: To assess relationship between the LAS and the probability of HFpEF in patients with dyspnea and paroxysmal AF. METHODS: The study included 205 consecutive patients (62 ± 10 years, 58% males) with dyspnea (NYHA≥II), paroxysmal AF and preserved LV ejection fraction (≥50%), who underwent speckle tracking echocardiography during sinus rhythm. Probability of HFpEF was estimated using H2FPEF and HFA-PEFF scores, which combine clinical characteristics, echocardiographic parameters and natriuretic peptides. RESULTS: Patients with high probability of HFpEF were significantly older, had higher body mass index, NT-proBNP, E/e', pulmonary artery pressure and larger LA volume index than patients in low-to-intermediate probability groups (all p < 0.05). All components of LAS and LA strain rate showed proportional impairment with increasing probability of HFpEF (all p < 0.05). Out of the speckle tracking-derived parameters, reservoir LAS showed the largest area under the curve (AUC = 0.78, p < 0.001) and the strongest independent predictive value (OR: 1.22, 95% CI 1.08-1.38) to identify patients with high probability of HFpEF. CONCLUSIONS: Reservoir LAS shows a high diagnostic performance to distinguish HFpEF from non-cardiac causes of dyspnea in symptomatic patients with paroxysmal AF.

Automatic estimation of a scale resolution in forensic images.

This paper proposes a new method for an automatic detection of a resolution of a scale or a ruler with graduation marks in the shoeprint images. The method creates a vector of the correlations estimated from the co-occurrence matrices for every row in a shoeprint image. The scale resolution is estimated from maxima in Fourier spectrum of the correlations' vectors. The proposed method is evaluated on over 500 images taken at crime scenes and in a forensics laboratory. The experimental results indicate the possibility of applying the proposed method to automatically estimate the scale resolution in forensic images. The automatic detection of a scale resolution could be used to automatically rescale a forensic image before the printing this image in "one-to-one" scale. Furthermore, the proposed method could be used to automatically rescale images to an equal scale thus allowing to compare the images digitally.

Bone marrow stem cell therapy for cardiac repair: challenges and perspectives.

UNLABELLED: Bone marrow (BM) stem cells can differentiate into multiple cell types, including vascular cells and, possibly, cardiac myocytes. Stem and progenitor cells are mobilized into the peripheral circulation early after myocardial infarction. Experimental evidence suggests that BM-derived cells injected into infarcted hearts can improve cardiac function. However, mechanisms underlying functional improvements remain unclear. Initial randomized, placebo-controlled trials in patients with acute myocardial infarction have provided controversial RESULTS: On the one hand, a modest but significant and sustained improvement in left ventricular function was observed in the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) study contributing to the better clinical course. Results of other studies were neutral. Differences in the study design, cell processing or timing of cell delivery might explain, in part, different outcomes among studies. Furthermore, studies in patients with chronic ischemic heart disease remain observational, and therapeutic effects using surrogate end-points needs to be demonstrated. Thus, there is a need for further coordinated research with well designed, hypothesis-driven clinical trials, in parallel with fundamental research aimed at understanding the mechanisms underlying the biological and functional effects of BM cell therapy for cardiac repair.

Wasted septal work in left ventricular dyssynchrony: a novel principle to predict response to cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) in heart failure is limited by many non-responders. This study explores whether degree of wasted left ventricular (LV) work identifies CRT responders. METHODS AND RESULTS: Twenty-one patients who received CRT according to guidelines were studied before and after 8 ± 3 months. By definition, segments that shorten in systole perform positive work, whereas segments that lengthen do negative work. Work was calculated from non-invasive LV pressure and strain by speckle tracking echocardiography. For each myocardial segment and for the entire LV, wasted work was calculated as negative work in percentage of positive work. LV wall motion score index (WMSI) was assessed by echocardiography. Response to CRT was defined as ≥15% reduction in end-systolic volume (ESV). Responder rate to CRT was 71%. In responders, wasted work for septum was 117 ± 102%, indicating more negative than positive work, and decreased to 14 ± 12% with CRT (P < 0.01). In the LV free wall, wasted work was 19 ± 16% and showed no significant change. Global LV wasted work decreased from 39 ± 21 to 17 ± 7% with CRT (P < 0.01). In non-responders, there were no significant changes. In multiple linear regression analysis, septal wasted work and WMSI were the only significant predictors of ESV reduction (ß = 0.14, P = 0.01; ß = 1.25, P = 0.03). Septal wasted work together with WMSI showed an area under the curve of 0.86 (95% confidence interval 0.71-1.0) for CRT response prediction. CONCLUSION: Wasted work in the septum together with WMSI was a strong predictor of response to CRT. This novel principle should be studied in future larger studies.

Effects of dobutamine on coronary stenosis physiology and morphology: comparison with intracoronary adenosine.

BACKGROUND: The mechanisms leading to dobutamine-induced ischemia are not fully understood. In the present study, we investigated the effects of high-dose intravenous dobutamine on morphological and physiological indexes of coronary stenoses. METHODS AND RESULTS: Twenty-two patients with normal left ventricular function and isolated coronary stenoses were studied. At catheterization, mean aortic pressure (P(a)), mean distal coronary pressure (P(d)), and P(d)/P(a) as an index of myocardial resistance were recorded at rest, after intracoronary adenosine, and during intravenous infusion of dobutamine (10 to 40 micrograms . kg(-1). min(-1)). Reference vessel diameter and minimal luminal diameter, as assessed by coronary angiography, did not change during dobutamine infusion compared with baseline (2.84+/-0.49 versus 2.77+/-0.41 mm and 1.35+/-0.38 versus 1. 27+/-0.31 mm, respectively; both P=NS). During peak dobutamine infusion, P(d) and P(d)/P(a) reached similar levels as during adenosine infusion (60+/-18 versus 59+/-18 mm Hg and 0.68+/-0.18 versus 0.68+/-0.17, respectively; all P=NS). In 9 patients, an additional bolus of intracoronary adenosine given at the peak dose of dobutamine failed to further decrease P(d)/P(a). Furthermore, in patients with dobutamine-induced wall motion abnormalities, the maximal decrease in P(d)/P(a) was similar during dobutamine and adenosine infusions. CONCLUSIONS: High-dose intravenous infusion of dobutamine does not modify the dimensions of the epicardial coronary stenosis. However, much like the direct coronary vasodilator adenosine, dobutamine fully exhausts myocardial resistance regardless of the presence of mechanical dysfunction.

Neuregulin in cardiac hypertrophy in rats with aortic stenosis. Differential expression of erbB2 and erbB4 receptors.

BACKGROUND: Neuregulins are a family of peptide growth factors that promote cell growth and viability. The potential role of neuregulin-erbB signaling in hypertrophic growth and later failure in the adult heart in vivo is not known. METHODS AND RESULTS: We used ribonuclease protection assays to quantify mRNA levels of neuregulin, erbB2, and erbB4 in left ventricular (LV) tissue and myocytes of normal rats and rats with aortic stenosis with pressure-overload hypertrophy 6 and 22 weeks after banding. At both stages of hypertrophy, Northern blot analyses of mRNA from LV myocytes showed upregulation of atrial natriuretic peptide, a molecular marker of hypertrophy (P<0.05). LV tissue neuregulin message levels were similar in animals with aortic stenosis compared with controls (P=NS) and were not detectable in myocytes. LV erbB2 and erbB4 message levels in LV tissue and myocytes were maintained during early compensatory hypertrophy in 6-week aortic stenosis animals compared with age-matched controls; in contrast, erbB2 and erbB4 message levels were depressed in 22-week aortic stenosis animals at the stage of early failure (both P<0.01 vs age-matched controls). Immunoblotting of erbB2 and erbB4 also showed normal protein levels in 6-week aortic stenosis animals compared with controls; however, erbB2 and erbB4 protein levels were depressed in 22-week aortic stenosis animals (48% decrease in erbB2, P<0.05, and 43% decrease in erbB4, P<0.01) relative to age-matched controls. CONCLUSIONS: The neuregulin receptors erbB2 and erbB4 are downregulated at both the message and protein levels at the stage of early failure in animals with chronic hypertrophy secondary to aortic stenosis. These data suggest a role for disabled erbB receptor signaling in the transition from compensatory hypertrophy to failure.

Chronic N(G)-nitro-L-arginine methyl ester-induced hypertension : novel molecular adaptation to systolic load in absence of hypertrophy.

BACKGROUND: Chronic N(G)-nitro-L-arginine methyl ester (L-NAME), which inhibits nitric oxide synthesis, causes hypertension and would therefore be expected to induce robust cardiac hypertrophy. However, L-NAME has negative metabolic effects on protein synthesis that suppress the increase in left ventricular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME-induced hypertension to test the hypothesis that adaptation to pressure overload occurs even when hypertrophy is suppressed. METHODS AND RESULTS: Male rats received L-NAME (50 mg. kg(-1). d(-1)) or no drug for 6 weeks. Rats with L-NAME-induced hypertension had levels of systolic wall stress similar to those of rats with aortic stenosis (85+/-19 versus 92+/-16 kdyne/cm). Rats with aortic stenosis developed a nearly 2-fold increase in LV mass compared with controls. In contrast, in the L-NAME rats, no increase in LV mass (1. 00+/-0.03 versus 1.04+/-0.04 g) or hypertrophy of isolated myocytes occurred (3586+/-129 versus 3756+/-135 microm(2)) compared with controls. Nevertheless, chronic pressure overload was not accompanied by the development of heart failure. LV systolic performance was maintained by mechanisms of concentric remodeling (decrease of in vivo LV chamber dimension relative to wall thickness) and augmented myocardial calcium-dependent contractile reserve associated with preserved expression of alpha- and beta-myosin heavy chain isoforms and sarcoplasmic reticulum Ca(2+) ATPase (SERCA-2). CONCLUSIONS: When the expected compensatory hypertrophic response is suppressed during L-NAME-induced hypertension, severe chronic pressure overload is associated with a successful adaptation to maintain systolic performance; this adaptation depends on both LV remodeling and enhanced contractility in response to calcium.

Abnormal epicardial coronary resistance in patients with diffuse atherosclerosis but "Normal" coronary angiography.

BACKGROUND: Coronary arteries without focal stenosis at angiography are generally considered non-flow-limiting. However, atherosclerosis is a diffuse process that often remains invisible at angiography. Accordingly, we hypothesized that in patients with coronary artery disease, nonstenotic coronary arteries induce a decrease in pressure along their length due to diffuse coronary atherosclerosis. METHODS AND RESULTS: Coronary pressure and fractional flow reserve (FFR), as indices of coronary conductance, were obtained from 37 arteries in 10 individuals without atherosclerosis (group I) and from 106 nonstenotic arteries in 62 patients with arteriographic stenoses in another coronary artery (group II). In group I, the pressure gradient between aorta and distal coronary artery was minimal at rest (1+/-1 mm Hg) and during maximal hyperemia (3+/-3 mm Hg). Corresponding values were significantly larger in group II (5+/-4 mm Hg and 10+/-8 mm Hg, respectively; both P<0.001). The FFR was near unity (0.97+/-0.02; range, 0.92 to 1) in group I, indicating no resistance to flow in truly normal coronary arteries, but it was significantly lower (0.89+/-0.08; range, 0.69 to 1) in group II, indicating a higher resistance to flow. In 57% of arteries in group II, FFR was lower than the lowest value in group I. In 8% of arteries in group II, FFR was <0.75, the threshold for inducible ischemia. CONCLUSION: Diffuse coronary atherosclerosis without focal stenosis at angiography causes a graded, continuous pressure fall along arterial length. This resistance to flow contributes to myocardial ischemia and has consequences for decision-making during percutaneous coronary interventions.

Fractional flow reserve in patients with prior myocardial infarction.

BACKGROUND: Fractional flow reserve (FFR), an index of coronary stenosis severity, can be calculated from the ratio of hyperemic distal to proximal coronary pressure. An FFR value of 0.75 can distinguish patients with normal and abnormal noninvasive stress testing in case of normal left ventricular function. The present study aimed at investigating the value of FFR in patients with a prior myocardial infarction. Methods and Results-- In 57 patients who had sustained a myocardial infarction >/=6 days earlier, myocardial perfusion single photon emission scintigraphy (SPECT) imaging and FFR were obtained before and after angioplasty. The sensitivity and specificity of the 0.75 value of FFR to detect flow maldistribution at SPECT imaging were 82% and 87%. The concordance between the FFR and SPECT imaging was 85% (P<0.001). When only truly positive and truly negative SPECT imaging were considered, the corresponding values were 87%, 100%, and 94% (P<0.001). Patients with positive SPECT imaging before angioplasty had a significantly lower FFR than patients with negative SPECT imaging (0.52+/-0.18 versus 0.67+/-0.16, P=0.0079) but a significantly higher left ventricular ejection fraction (63+/-10% versus 52+/-10%, P=0.0009) despite a similar degree of diameter stenosis (67+/-13% versus 68+/-16%, P=NS). A significant inverse correlation was found between LVEF and FFR (R=0.29, P=0.049). CONCLUSIONS: The present data indicate (1) that the 0.75 cutoff value of FFR to distinguish patients with positive from patients with negative SPECT imaging is valid after a myocardial infarction and (2) that for a similar degree of stenosis, the value of FFR depends on the mass of viable myocardium.

Left ventricular hypertrophy in ascending aortic stenosis mice: anoikis and the progression to early failure.

BACKGROUND: To determine potential mechanisms of the transition from hypertrophy to very early failure, we examined apoptosis in a model of ascending aortic stenosis (AS) in male FVB/n mice. METHODS AND RESULTS: Compared with age-matched controls, 4-week and 7-week AS animals (n=12 to 16 per group) had increased ratios of left ventricular weight to body weight (4.7+/-0.7 versus 3.1+/-0.2 and 5. 7+/-0.4 versus 2.7+/-0.1 mg/g, respectively, P<0.05) with similar body weights. Myocyte width was also increased in 4-week and 7-week AS mice compared with controls (19.0+/-0.8 and 25.2+/-1.8 versus 14. 1+/-0.5 microm, respectively, P<0.01). By 7 weeks, AS myocytes displayed branching with distinct differences in intercalated disk size and staining for beta(1)-integrin on both cell surface and adjacent extracellular matrix. In vivo left ventricular systolic developed pressure per gram as well as endocardial fractional shortening were similar in 4-week AS and controls but depressed in 7-week AS mice. Myocyte apoptosis estimated by in situ nick end-labeling (TUNEL) was extremely rare in 4-week AS and control mice; however, a low prevalence of TUNEL-positive myocytes and DNA laddering were detected in 7-week AS mice. The specificity of TUNEL labeling was confirmed by in situ ligation of hairpin oligonucleotides. CONCLUSIONS: Our findings indicate that myocyte apoptosis develops during the transition from hypertrophy to early failure in mice with chronic biomechanical stress and support the hypothesis that the disruption of normal myocyte anchorage to adjacent extracellular matrix and cells, a process called anoikis, may signal apoptosis.

Fractional flow reserve to determine the appropriateness of angioplasty in moderate coronary stenosis: a randomized trial.

BACKGROUND: PTCA of a coronary stenosis without documented ischemia at noninvasive stress testing is often performed, but its benefit is unproven. Coronary pressure-derived fractional flow reserve (FFR) is an invasive index of stenosis severity that is a reliable substitute for noninvasive stress testing. A value of 0.75 identifies stenoses with hemodynamic significance. METHODS AND RESULTS: In 325 patients for whom PTCA was planned and who did not have documented ischemia, FFR of the stenosis was measured. If FFR was >0.75, patients were randomly assigned to deferral (deferral group; n=91) or performance (performance group; n=90) of PTCA. If FFR was <0.75, PTCA was performed as planned (reference group; n=144). Clinical follow-up was obtained at 1, 3, 6, 12, and 24 months. Event-free survival was similar between the deferral and performance groups (92% versus 89% at 12 months and 89% versus 83% at 24 months) but was significantly lower in the reference group (80% at 12 months and 78% at 24 months). In addition, the percentage of patients free from angina was similar between the deferral and performance groups (49% versus 50% at 12 months and 70% versus 51% at 24 months) but was significantly higher in the reference group (67% at 12 and 80% at 24 months). CONCLUSIONS: In patients with a coronary stenosis without evidence of ischemia, coronary pressure-derived FFR identifies those who will benefit from PTCA.

Quantitative coronary angiography in predicting functional significance of stenoses in an unselected patient cohort.

OBJECTIVES: This study investigated the value of quantitative coronary angiography for predicting coronary flow reserve, as calculated from the transstenotic pressure gradient in a large, unselected patient cohort. BACKGROUND: In patients with extensive coronary artery disease, quantitative coronary angiographic findings fail to correlate with functional variables of coronary stenoses. New developments in pressure-monitoring wire technology permitted validation in humans of the concept of myocardial fractional flow reserve as assessed from coronary pressure measurements. METHODS: One hundred ten patients with normal left ventricular function were studied in the setting of coronary angioplasty. Quantitative coronary angiography was performed on-line using the ACA system. Myocardial and coronary fractional flow reserve were calculated from aortic and distal coronary pressures during maximal coronary hyperemia. RESULTS: When data before and after angioplasty were pooled, a curvilinear relation was found between myocardial fractional flow reserve and both diameter stenosis (r = 0.79) and minimal lumen diameter (r = 0.82), and a linear relation was found between myocardial fractional flow reserve and angiographic stenosis flow reserve (r = 0.78). Correlations between quantitative angiographic and pressure-derived indexes, although significant, were characterized by a large dispersion of the values of myocardial fractional flow reserve for a similar angiographic degree of stenosis. Nevertheless, the sensitivity and specificity of a minimal lumen diameter < 1.5 mm to predict myocardial fractional flow reserve < 0.72 were 96% and 89%, respectively. The corresponding values for a diameter stenosis > 50% were 93% and 85%, respectively. CONCLUSIONS: 1) In an unselected patient cohort, geometric indexes of stenosis severity derived from quantitative coronary angiography correlate significantly with physiologic variables, although these relations are imprecise in individual patients. 2) Nevertheless, the diagnostic accuracy of quantitative coronary angiography in predicting myocardial fractional flow reserve < 0.72 is high and allows its use for clinical decision making in the individual patient during diagnostic or interventional procedures.

Chronic L-arginine treatment increases cardiac cyclic guanosine 5'-monophosphate in rats with aortic stenosis: effects on left ventricular mass and beta-adrenergic contractile reserve.

OBJECTIVES: We tested the hypothesis that nitric oxide (NO) cyclic guanosine 5'-monophosphate (GMP) signaling is deficient in pressure overload hypertrophy due to ascending aortic stenosis, and that long-term L-arginine treatment will increase cardiac cyclic GMP production and modify left ventricular (LV) pressure overload hypertrophy and beta-adrenergic contractile response. BACKGROUND: Nitric oxide cyclic GMP signaling is postulated to depress vascular growth, but its effects on cardiac hypertrophic growth are controversial. METHODS: Forty control rats and 40 rats with aortic stenosis left ventricular hypertrophy ([LVH] group) were randomized to receive either L-arginine (0.40 g/kg/day) or no drug for 6 weeks. RESULTS: The dose of L-arginine did not alter systemic blood pressure. Animals with LVH had similar LV constitutive nitric oxide synthase (cNOS) mRNA and protein levels, and LV cyclic GMP levels as compared with age-matched controls. In rats with LVH L-arginine treatment led to a 35% increase in cNOS protein levels (p = 0.09 vs untreated animals with LVH) and a 1.7-fold increase in LV cyclic GMP levels (p < 0.05 vs untreated animals with LVH). However, L-arginine treatment did not suppress LVH in the animals with aortic stenosis. In contrast, in vivo LV systolic pressure was depressed in L-arginine treated versus untreated rats with LVH (163 +/- 16 vs 198 +/- 10 mm Hg, p < 0.05). In addition, the contractile response to isoproterenol was blunted in both isolated intact hearts and isolated myocytes from L-arginine treated rats with LVH compared with untreated rats with LVH. This effect was mediated by a blunted increase in peak systolic intracellular calcium in response to beta-adrenergic stimulation. CONCLUSIONS: Left ventricular hypertrophy due to chronic mechanical systolic pressure overload is not characterized by a deficiency of LV cNOS and cyclic GMP levels. In rats with aortic stenosis, L-arginine treatment increased cardiac levels of cyclic GMP, but it did not modify cardiac mass in rats with aortic stenosis. However, long-term stimulation of NO-cyclic GMP signaling depressed in vivo LV systolic function in LVH rats and markedly blunted the contractile response to beta-adrenergic stimulation.

Long-term follow-up after deferral of percutaneous transluminal coronary angioplasty of intermediate stenosis on the basis of coronary pressure measurement.

OBJECTIVES: This study sought to determine the safety of deferral of percutaneous transluminal coronary angioplasty (PTCA) of angiographically intermediate but functionally nonsignificant stenosis, as assessed by coronary pressure measurement and myocardial fractional flow reserve (FFRmyo). BACKGROUND: Decision making in patients with chest pain and intermediate coronary stenosis remains difficult. In these cases it is unclear whether the risk of an intervention and the potentially subsequent restenosis outweigh the future risk of an event if the lesion remains untreated. FFRmyo is a lesion-specific functional index of epicardial stenosis severity that accurately distinguishes stenoses associated with inducible ischemia. METHODS: Retrospective analysis and follow-up was performed in 100 consecutive patients referred to our centers for PTCA of an intermediate stenosis but in whom the planned intervention was deferred on the basis of an FFRmyo > or = 0.75. RESULTS: During a follow-up period of 18+/-13 months (mean +/- SD, range 3 to 42), two patients died of noncardiac causes. Ninety patients remained free of any coronary events, and their average Canadian Cardiovascular Society class decreased from 2.0+/-1.2 at baseline to 0.7+/-0.9 at follow-up (p < 0.0001). A coronary event occurred in eight patients and was target-vessel related in four. CONCLUSIONS: In patients with chest pain referred for PTCA of an intermediate stenosis, deferral of the intervention on the basis of an FFRmyo > or = 0.75 is safe and is associated with a much lower clinical event rate than if the procedure had been performed as initially planned in these patients.

Dobutamine-induced wall motion abnormalities: correlations with myocardial fractional flow reserve and quantitative coronary angiography.

OBJECTIVES: This study evaluated both the relation between dobutamine-induced wall motion abnormalities and the physiologic and morphologic features of epicardial coronary artery stenoses and the impact of the extent of the area at risk on the sensitivity of dobutamine echocardiography. BACKGROUND: The accuracy of dobutamine echocardiography has traditionally been assessed by comparing results with stenosis geometry. Myocardial fractional flow reserve is a functional index of coronary stenosis severity that takes into account both antero-grade and collateral flow and may therefore be a more appropriate standard for comparison. METHODS: Seventy-five patients with normal left ventricular function, good echocardiographic images and an isolated coronary stenosis underwent, within 6 h, dobutamine echocardiography, quantitative coronary angiography and intracoronary pressure measurements. Myocardial fractional flow reserve was calculated as the ratio of mean hyperemic distal coronary to aortic pressure. RESULTS: The degree of dobutamine-induced dyssynergy correlated significantly with percent diameter stenosis (r = 0.68), area stenosis (r = 0.68) and minimal lumen diameter (r = -0.60) and markedly better with myocardial fractional flow reserve (r = -0.77). However, marked dispersion of the individual data was observed. The sensitivity of dobutamine echocardiography in detecting lesions with a minimal lumen diameter < or = 1 mm and diameter stenosis > or = 50% was 83% and 80%, respectively. All but one patient with a myocardial fractional flow reserve >0.75 had a normal stress test result. Among patients with a myocardial fractional flow reserve < or = 0.75, the sensitivity of dobutamine echocardiography was significantly lower for lesions in vessels with a reference diameter < or = 2.6 mm than for lesions in larger vessels (58% vs. 90%, p = 0.008). CONCLUSIONS: 1) The magnitude of wall motion abnormalities induced by dobutamine infusion correlates with angiographic and, more closely, with functional indexes of stenosis severity, even though a wide scatter is observed. 2) In patients with a functionally significant stenosis, the amount of myocardium at risk is a critical determinant of the accuracy of dobutamine echocardiography.

Gender differences in molecular remodeling in pressure overload hypertrophy.

OBJECTIVES: The objective of this study was to examine gender differences in left ventricular (LV) function and expression of cardiac genes in response to LV pressure overload due to ascending aortic stenosis in rats. BACKGROUND: Clinical studies have documented gender differences in the pattern of adaptive LV hypertrophy. Whether these differences result from intrinsic differences in molecular adaptation to pressure overload between men and women, or are related to other factors is not known. METHODS: Male (n = 8) and female (n = 8) Wistar rats underwent ascending aortic stenosis and were studied 6 weeks after banding with gender-matched control rats (male n = 7; female n = 7). The LV contractile reserve was examined in isolated hearts from each group. We compared LV messenger ribonucleic acid (mRNA) levels of atrial natriuretic factor (ANF), beta-myosin heavy chain, sarcoplasmic reticulum Ca2+-adenosine triphosphatase (ATPase) and Na+-Ca2+ exchanger. Reverse transcriptase polymerase chain reaction was used to identify estrogen receptor transcript in cardiac myocytes and LV tissue. RESULTS: The magnitude of LV hypertrophy (LVH) and systolic wall stress were similar in male and female animals with LVH. Male LVH hearts demonstrated a depressed contractile reserve; in contrast, contractile reserve was preserved in female LVH hearts. The expression of beta-myosin heavy chain and ANF mRNA was greater in male versus female LVH hearts. Sarcoplasmic reticulum Ca2+-ATPase mRNA levels were depressed in male LVH but not in female LVH compared with control rats, and Na+-Ca2+ exchanger mRNA levels were increased similarly in both male and female LVH hearts. Estrogen receptor transcript was detected in both adult male and female cardiac myocytes and LV tissue. CONCLUSIONS: There are significant gender differences in the LV adaptation to pressure overload despite a similar degree of LVH and systolic wall stress in male and female rats. There is the potential for estrogen signaling through the adult myocyte estrogen receptor in both male and female rats to contribute to gender differences in gene expression in pathologic hypertrophy.

Myocardial perfusion and oxygen consumption in reperfused noninfarcted dysfunctional myocardium after unstable angina: direct evidence for myocardial stunning in humans.

OBJECTIVES: To positively establish the diagnosis of myocardial stunning in patients with unstable angina and persistent wall motion abnormalities after reperfusion by coronary angioplasty. BACKGROUND: Although myocardial stunning is thought to occur in several clinical conditions, definite proof of its existence in humans is still lacking, owing to the difficulty of measuring myocardial blood flow (MBF) in absolute terms. METHODS: We studied 14 patients with unstable angina due to proximal left anterior descending coronary artery disease who presented persistent anterior wall motion abnormalities despite revascularization of the culprit lesion by percutaneous coronary angioplasty (PTCA) and who did not have clinical evidence of necrosis. Dynamic positron emission tomography (PET) with [13N]-ammonia and [11C]-acetate was performed 48 h after PTCA to determine absolute MBF and oxygen consumption (MVO2). Regional wall thickening and regional cardiac work were determined using two-dimensional echocardiography. Improvement of segmental wall motion abnormalities was followed for a median of 4 months (1.5 to 14 months). RESULTS: As judged from the changes in segmental wall motion score, regional dysfunction was spontaneously reversible in 12/14 patients and improved from 2.2 +/- 0.3 to 1.2 +/- 0.3 at late follow-up (p < 0.001). With PET, [13N]-ammonia MBF was similar among dysfunctional and remote normally contracting segments (85 +/- 29 vs. 99 +/- 20 ml x min (-1) x 100g(-1), p = not significant [n.s.]), thus demonstrating a perfusion-contraction mismatch. Despite the reduced contractile function, dysfunctional myocardium presented near normal levels of MVO2 (6.5 +/- 4.2 vs. 8.0 +/- 1.9 ml x min (-1)x 100g(-1), p = n.s.). Consequently, the regional myocardial efficiency (regional work divided by MVO2) of the dysfunctional myocardium was found to be markedly decreased as compared with normally contracting myocardium (6 +/- 6% vs. 26 +/- 6%, p < 0.001). CONCLUSIONS: This study demonstrates that human dysfunctional myocardium capable of spontaneously recovering contractile function after unstable angina endures a state of perfusion-contraction mismatch. These data for the first time provide unequivocal direct evidence for the existence of acute myocardial stunning in humans.

Epicardial catheter-based ventricular reconstruction (ECVR) in a patient with ischemic heart failure and an anteroapical aneurysm.

Extended anterior myocardial infarction (MI) is frequently followed by left ventricular (LV) remodeling ensuing in heart failure and aneurysmatic transformation of the infarcted myocardial segment. Therapies that attenuate or reverse pathological LV remodeling have been shown to improve functional status and outcomes. This case reports our recent experience with a catheter based technique for ventricular restoration.

Comparison of exercise electrocardiography and dobutamine echocardiography with invasively assessed myocardial fractional flow reserve in evaluation of severity of coronary arterial narrowing.

This study compares side-by-side exercise electrocardiography and dobutamine echocardiography with an invasively assessed index of myocardial flow (pressure-derived myocardial fractional flow reserve). The data show that ST-segment depression > or = 0.1 mV and the occurrence of new wall motion abnormalities during dobutamine infusion reflect a similar impairment of myocardial blood flow.