Javier Bermejo

In-Hospital Outcome of Elderly Patients With Acute Inferior Myocardial Infarction and Right Ventricular Involvement

BACKGROUND There are some specific high-risk subgroups of patients with acute inferior myocardial infarction, such as older patients and those with right ventricular involvement. However, the clinical implications of right ventricular infarction in elderly subjects have not been studied previously. METHODS AND RESULTS To determine the clinical impact of right ventricular involvement in elderly patients with inferior myocardial infarction, we studied the in-hospital outcome of 198 consecutive patients > or = 75 years of age with a first acute inferior myocardial infarction according to the presence of ECG or echocardiographic criteria of right ventricular infarction. In patients with right ventricular involvement (41%), in-hospital case fatality rate was 47% (mainly because of nonreversible low cardiac output cardiogenic shock) compared with 10% in patients without right ventricular involvement (P<.001). Patients with right ventricular involvement also had a significantly higher incidence of cardiogenic shock (32% versus 5%), which was independent of left ventricular ejection fraction, complete AV block (33% versus 9%), and interventricular septal rupture (9% versus 0%). After adjustment for age, sex, diabetes, shock on admission, left ventricular systolic dysfunction, and complete AV block, right ventricular infarction remained a powerful independent predictor of in-hospital death (adjusted odds ratio, 4.0; 95% confidence interval, 1.3 to 14.2). CONCLUSIONS Elderly patients with acute inferior myocardial infarction have a substantially increased risk of death during hospitalization when right ventricular involvement is present. The poorer outcome is due mainly to the high incidence of cardiogenic shock and its infrequent reversibility.

Effects of dobutamine on doppler echocardiographic indexes of aortic stenosis

OBJECTIVES This study sought to assess the diagnostic implications of the flow dependence of Doppler echocardiographic indexes of aortic valve stenosis. BACKGROUND Although valve area has been shown to change with alterations in flow rate, the diagnostic consequences of this phenomenon remain unknown. Valve resistance has been suggested as a more stable index for evaluating aortic stenosis. METHODS A low dose dobutamine protocol was performed in 35 patients with aortic stenosis. Hemodynamic indexes were obtained by Doppler echocardiography at baseline and at each dobutamine dose. RESULTS As a result of the shortening of the systolic ejection period, flow increased from (mean +/- SD) 164 +/- 48 to 229 +/- 102 ml/s (p < 0.0001). At peak flow, valve area increased by 28% (from 0.5 +/- 0.2 to 0.6 +/- 0.3 cm2, p < 0.0001), whereas valve resistance decreased by 4% (from 498 +/- 252 to 459 +/- 222 dynes.s.cm-5, p = 0.04). This observed change in resistance was smaller than that for valve area (p < 0.01). The flow dependence of valve area varied among individual patients (p < 0.0001). Multivariate analysis identified calcific degenerative etiology (beta 0.29, p = 0.002), left ventricular velocity of fiber shortening (beta 0.22, p = 0.01), baseline flow (beta -0.28, p = 0.04) and amount of flow increased induced by dobutamine (beta 0.90, p < 0.0001) as factors related to valve area flow dependence. CONCLUSIONS Although all Doppler echocardiographic indexes of aortic stenosis are affected by flow, valve resistance is more stable than valve area under dobutamine-induced hemodynamic changes. Baseline valve area may be unreliable in patients with calcific degenerative aortic stenosis and low output states.

Mechanisms of Residual Lumen Stenosis After High-Pressure Stent Implantation A Quantitative Coronary Angiography and Intravascular Ultrasound Study

BACKGROUND Intravascular ultrasound (IVUS) studies have demonstrated that stents are frequently suboptimally expanded despite the use of high pressures for deployment. The purpose of this study was to identify the mechanisms responsible for such residual lumen stenosis. METHODS AND RESULTS Fifty-seven lesions from 50 patients treated with high-pressure (median+/-interquartile range, 14+/-2 atm) elective (44 de novo, 13 restenotic lesions) stenting were prospectively studied (29 Wiktor, Medtronic; 28 Palmaz-Schatz, Cordis Corp). Balloon subexpansion was calculated as the difference between maximal and minimal balloon cross-sectional areas at peak pressure measured by automatic edge detection; elastic recoil was calculated as the difference between minimal measured balloon size and IVUS-derived minimal lumen area within the stent. Angiographic residual diameter stenosis was 10+/-13% (reference diameter, 3.1+/-0.7 mm; balloon to artery ratio, 1.12+/-0.23) and IVUS-derived stent expansion was 80+/-28%. However, although balloon nominal size was 9.6+/-1.3 mm2 and maximal balloon size measured inside the coronary lumen was 12.5+/-3.2 mm2, final stent minimal lumen area was only 7.1+/-2.2 mm2. Balloon subexpansion of 4.0+/-1.8 mm2 (33%) and elastic recoil of 1.6+/-2.3 mm2 (20%) (both P<0.0001) were the two mechanisms responsible for residual luminal stenosis. Wiktor stent and peak inflation pressure correlated with balloon subexpansion, whereas Wiktor stent, de novo lesion, and minimal lumen area at baseline correlated with elastic recoil. CONCLUSIONS Despite high-pressure deployment, lumen dimensions after stenting are only 57% of maximal achievable. Inadequate balloon expansion and elastic recoil are responsible for residual lumen stenosis, suggesting that plaque characteristics and stent resistance deserve further investigation.

Role of transesophageal echocardiography in the assessment of patients with blunt chest trauma: Correlation of echocardiographic findings with the electrocardiogram and creatine kinase monoclonal antibody measurements

OBJECTIVES This study was designed to evaluate the usefulness of transesophogeal echocardiography (TEE) for detecting cardiac damage after blunt chest trauma (BCT). BACKGROUND Multiple methods have been used to detect cardiac damage after a BCT, but none has been demonstrated to be sensitive, specific, and feasible enough. METHODS This multicenter prospective trial was designed to evaluate the usefulness of TEE in the assessment of patients with BCT and to compare the TEE findings with those provided by the electrocardiogram (ECG) and cardiac isoenzymes assay. One hundred seventeen consecutive patients with a significant BCT were enrolled. A TEE was performed in each patient. Serial ECGs and plasma profiles of creatine kinase (CK) and CK-monoclonal antibody (MB) were obtained. RESULTS Sixty-six (56%) patients had pathologic findings in the TEE attributed to the BCT (group A). In the remaining 51 (44%) patients the TEE was normal (group B). An abnormal ECG was more frequent in group A (59% vs 24%; p < 0.001), and the serum CK-MB peak level was also higher in group A (174 +/- 30 U/L vs 93 +/- 21 U/L; p = 0.05). Relative to pathologic TEE findings, the sensitivity and specificity of an abnormal ECG were 59% and 73% and of high CK-MB with CK-MB/CK > 5% were 64% and 52%, respectively. CONCLUSIONS We conclude that TEE can be routinely and safely performed for diagnosing cardiac injuries after a BCT and plays an important role in the evaluation and treatment of these patients. EGG and CK-MB assay are not good methods for detecting cardiac damage in this setting.

Diet-Induced Aortic Valve Disease in Mice Haploinsufficient for the Notch Pathway Effector RBPJK/CSL

Objective—Calcific aortic valve disease is similar to atherosclerosis in that both diseases result from chronic inflammation and endothelial dysfunction. Heterozygous NOTCH1 mutations have been associated to calcific aortic disease and a bicuspid aortic valve. We investigated whether mice with genetic inactivation of the Notch signaling pathway are prone to develop valve disease when exposed to a predisposing diet. Methods and Results—Using Doppler echocardiography, histology, immunohistochemistry, quantitative gene expression analysis, and cell culture assays, we examined the effect of a hypercholesterolemic diet supplemented with vitamin D on mice heterozygous for null mutations in the Notch1 receptor or the effector transcription factor gene RBPJk. After 16 weeks on the hyperlipidemic diet, calcific aortic disease was detected in heterozygous RBPJk mice. Analysis of valve leaflets revealed macrophage infiltration, enhanced collagen deposition, proosteogenic protein expression, and calcification. Heterozygous null Notch1 mice displayed milder histopathologic changes and did not develop any significant hemodynamic disturbance. Valvular disease correlated with reduced expression of the Notch target gene Hey1 in valves of RBPJk heterozygous mice fed the hyperlipidemic diet. Consistent with the in vivo data, Notch signaling inhibition in porcine valve interstitial cells led to downregulation of HEY1 transcription, activation of osteogenic markers, and increased calcified nodule formation. Conclusion—We show that Notch signaling disruption via RBPJk heterozygous inactivation results in aortic valve disease. Notch1 heterozygous mice do not show functional impairment, suggesting that additional Notch receptors may be involved in aortic valve homeostasis and disease. Our data establish a genetic mouse model of calcific aortic valve disease and may help to identify a patient population with reduced valvular NOTCH signaling at risk for developing this disease.

Association between self-replicating calcifying nanoparticles and aortic stenosis: a possible link to valve calcification.

AIMS Among various hypotheses proposed for pathological tissue calcification, recent evidence supports the possibility that self-replicating calcifying nanoparticles (CNPs) can contribute to such calcification. These CNPs have been detected and isolated from calcified human tissues, including blood vessels and kidney stones, and are referred to as nanobacteria. We evaluated calcific aortic valves for the presence of CNP. METHODS AND RESULTS Calcific aortic valves were obtained from 75 patients undergoing surgical valve replacement. The control group was formed by eight aortic valves corresponding to patients with heart transplants. In the microbiology laboratory, valves were screened for CNP using a 4-6 weeks specific culture method. The culture for CNP was positive in 48 of the 75 valves with aortic stenosis (64.0%) in comparison with zero of eight (0%) for the control group (P = 0.0005). The observation of cultures by way of scanning electron microscopy highlighted the resemblance in size and morphology of CNP. CONCLUSION Self-replicating calcific nanometer-scale particles, similar to those described as CNP from other calcific human tissues, can be cultured and visualized from calcific human aortic valves. This finding raises the question as to whether CNP contribute to the pathogenesis of the disease or whether they are only innocent bystanders.

Spatio-temporal mapping of intracardiac pressure gradients. A solution to Euler's equation from digital postprocessing of color Doppler M-mode echocardiograms.

Doppler assessment of intracardiac pressure gradients using the simplified Bernoulli equation is inaccurate in the absence of a restricted orifice. The purpose of this study is to develop a new general method to map instantaneous pressure gradients inside the heart using Doppler echocardiography. Color Doppler M-mode recordings are digitally postprocessed with a software algorithm that decodes flow velocity and fits a bivariate spatio-temporal tensor-product smoothing spline. Temporal and spatial accelerations are then calculated by analytical derivation of the fitted velocity data, allowing solution of both inertial and convective terms of Eulers equation. A database of 39 transmitral inflow and transaortic outflow color Doppler M-mode recordings from 20 patients with a number of cardiac conditions was analysed, along with matched pulsed-wave spectral recordings. A close agreement was observed between the spectral and postprocessed color Doppler velocity values (error = 0.8 +/- 11.7 cm/s), validating the data decoding and fitting process. Spatio-temporal pressure-gradient maps were obtained from all studies, allowing visualisation of instantaneous pressure gradients from the atrium to the apex during left ventricular filling, and from the apex to the outflow tract during ejection. Instantaneous pressure differences between localised intracardiac sample points closely matched previously published catheterization findings, both in magnitude and waveform shape. Our method shows that intracardiac instantaneous pressure gradients can be analysed noninvasively using color Doppler M-mode echocardiography combined with image postprocessing methods.

Contribution of the Diastolic Vortex Ring to Left Ventricular Filling

BACKGROUND Intraventricular fluid dynamics can be assessed clinically using imaging. The contribution of vortex structures to left ventricular (LV) diastolic function has never been quantified in vivo. OBJECTIVES This study sought to understand the impact of intraventricular flow patterns on filling and to assess whether impaired fluid dynamics may be a source of diastolic dysfunction. METHODS Two-dimensional flow velocity fields from color Doppler echocardiographic sequences were obtained in 20 patients with nonischemic dilated cardiomyopathy (NIDCM), 20 patients with hypertrophic cardiomyopathy (HCM), and 20 control healthy volunteers. Using a flow decomposition method, we isolated the rotational velocity generated by the vortex ring from the surrounding flow in the left ventricle. RESULTS The vortex was responsible for entering 13 ± 6% of filling volume in the control group and 19 ± 8% in the NIDCM group (p = 0.004), but only 5 ± 5% in the HCM group (p < 0.0001 vs. controls). Favorable vortical effects on intraventricular pressure gradients were observed in the control and NIDCM groups but not in HCM patients. Differences in chamber sphericity explained variations in the vortex contribution to filling between groups (p < 0.005). CONCLUSIONS The diastolic vortex is responsible for entering a significant fraction of LV filling volume at no energetic or pressure cost. Thus, intraventricular fluid mechanics are an important determinant of global chamber LV operative stiffness. Reduced stiffness in NIDCM is partially related to enhanced vorticity. Conversely, impaired vortex generation is an unreported mechanism of diastolic dysfunction in HCM and probably other causes of concentric remodeling.

Effects of angiotensin converting enzyme inhibitors in hypertensive patients with aortic valve stenosis: a drug withdrawal study

Objective: To determine the effects of angiotensin converting enzyme (ACE) inhibitors in hypertensive patients with aortic valve stenosis (AS). Design: Observational, drug withdrawal, single blinded study, with randomisation of the order of tests. Setting: Hypertension and asymptomatic AS. Patients and interventions: 20 patients (aged 73 (9) years, valve area 0.7 (0.3) cm2, left ventricular ejection fraction ⩾ 45%) were enrolled. Each patient underwent two sets of tests (with and without taking the drug), each of which included clinical evaluation, Doppler echocardiogram, and symptom limited exercise echocardiography. Main outcome measures: Functional and haemodynamic variables while taking and not taking ACE inhibitors. Results: Drug intervention induced no change in patients’ subjective functional class. While taking ACE inhibitors, patients had a lower systolic blood pressure (140 (18) mm Hg with ACE inhibitors v 159 (12) mm Hg without ACE inhibitors, p  =  0.02), a higher mean pressure gradient (34 (15) mm Hg v 28 (18) mm Hg, p  =  0.037), and a higher left ventricular stroke work loss (19 (6)% v 14 (10)%, p  =  0.009). Other baseline functional and haemodynamic parameters were unmodified. Five patients had an abnormal blood pressure response during one of the exercise tests (two patients while taking the drug and three patients while not taking the drug). When taking ACE inhibitors, patients had a higher stroke volume at peak stress (59 (11) ml v 54 (25) ml, p  =  0.046). All other stress variables remained constant. Conclusions: In AS, the afterload relief caused by ACE inhibitors is blunted by a parallel increase in the pressure gradient. However, ACE inhibitors favourably affect stress haemodynamic function in most hypertensive patients with AS and should not be discontinued.

Recommendations on the echocardiographic assessment of aortic valve stenosis: A focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography

Echocardiography is the key tool for the diagnosis and evaluation of aortic stenosis. Because clinical decision-making is based on the echocardiographic assessment of its severity, it is essential that standards are adopted to maintain accuracy and consistency across echocardiographic laboratories. Detailed recommendations for the echocardiographic assessment of valve stenosis were published by the European Association of Echocardiography and the American Society of Echocardiography in 2009. In the meantime, numerous new studies on aortic stenosis have been published with particular new insights into the difficult subgroup of low gradient aortic stenosis making an update of recommendations necessary. The document focuses in particular on the optimization of left ventricular outflow tract assessment, low flow, low gradient aortic stenosis with preserved ejection fraction, a new classification of aortic stenosis by gradient, flow and ejection fraction, and a grading algorithm for an integrated and stepwise approach of artic stenosis assessment in clinical practice.