Dan Gilon

Choice of computed tomography, transesophageal echocardiography, magnetic resonance imaging, and aortography in acute aortic dissection: International Registry of Acute Aortic Dissection (IRAD).

For acute aortic dissection, CT is selected most frequently worldwide as the initial test, followed by TEE. Aortography and MRI are performed much less often. More than two thirds of the patients required ≥2 imaging tests.

Acute type A aortic dissection in the elderly: clinical characteristics, management, and outcomes in the current era

OBJECTIVES We sought to evaluate the clinical characteristics, management, and outcomes of elderly patients with acute type A aortic dissection. BACKGROUND Few data exist on the clinical manifestations and outcomes of acute type A aortic dissection in an elderly patient cohort. METHODS We categorized 550 patients with type A aortic dissection enrolled in the International Registry of Acute Aortic Dissection into two age strata (<70 and >or=70 years) and compared their clinical features, management, and in-hospital events. RESULTS Thirty-two percent of patients with type A dissection were aged >or=70 years. Marfan syndrome was exclusively associated with dissection in the young, whereas hypertension, atherosclerosis and iatrogenic dissection predominated in older patients. Typical symptoms (abrupt onset of chest or back pain) and signs (aortic regurgitation murmur or pulse deficits) of dissection were less common among the elderly. Fewer elderly patients were managed surgically than younger patients (64% vs. 86%, p < 0.0001). Hypotension occurred more frequently (46% vs. 32%, p = 0.002) and focal neurologic deficits less frequently (18% vs. 26%, p = 0.04) among the elderly. In-hospital mortality was higher among older patients (43% vs. 28%, p = 0.0006). Logistic regression analysis identified age >or=70 years as an independent predictor of hospital death for acute type A aortic dissection (odds ratio 1.7, 95% confidence interval 1.1-2.8; p = 0.03). CONCLUSIONS Our study shows significant differences between older (age >or=70 years) and younger (age <70 years) patients with acute type A aortic dissection in their clinical characteristics, management, and hospital outcomes. Future research should evaluate strategies to improve outcomes in this high-risk elderly cohort.

Iatrogenic aortic dissection

Given the difference in risk factors, clinical presentation, and outcomes, clinicians should be vigilant for the presence of iatrogenic AD, particularly in those patients with unexplained hemodynamic instability or myocardial ischemia following invasive vascular procedures or CABG.

Differences in Clinical Presentation, Management, and Outcomes of Acute Type A Aortic Dissection in Patients With and Without Previous Cardiac Surgery

Background—There are less data on the clinical and diagnostic imaging characteristics, management, and outcomes of patients with previous cardiac surgery (PCS) presenting with acute type A aortic dissection (AAD). Methods and Results—In 617 patients with AAD, we evaluated the differences in the clinical characteristics, management, and in-hospital outcomes of the cohorts with and without PCS. A history of PCS was present in 100 of 617 patients. Patients with PCS were more likely to be males (P=0.02), older (P=0.014), and to have a history of previous aortic dissection (P<0.001) or aneurysms (P<0.001). In contrast, PCS patients were less likely to have presenting chest pain (P<0.001). Cardiac tamponade was less common in PCS patients (P=0.007). Fewer AAD patients with PCS underwent surgical repair (P=0.001). Hospital mortality was not adversely influenced by PCS (odds ratio [OR], 1.46; 95% confidence interval [CI], 0.81 to 2.63), but a trend for increased death was seen in patients with previous aortic valve replacement (AVR) (OR, 2.31; 95% CI, 0.98 to 5.43). Age70 years or older, previous AVR, shock, and renal failure identified PCS patients at risk for death. Conclusions—Our study highlights differences in clinical characteristics, management, and outcomes of AAD patients with PCS. Importantly, PCS, with the exception of previous AVR, does not adversely influence early outcomes of AAD patients, including those undergoing surgical repair. However, because of otherwise dismal outcomes with medical management of AAD, our data indicate that a history of PCS (even that of previous AVR) should not preclude physicians from recommending surgical correction of type A aortic dissection in appropriate patients.

Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation

A key energy-saving adaptation to chronic hypoxia that enables cardiomyocytes to withstand severe ischemic insults is hibernation, i.e., a reversible arrest of contractile function. Whereas hibernating cardiomyocytes represent the critical reserve of dysfunctional cells that can be potentially rescued, a lack of a suitable animal model has hampered insights on this medically important condition. We developed a transgenic mouse system for conditional induction of long-term hibernation and a system to rescue hibernating cardiomyocytes at will. Via myocardium-specific induction (and, in turn, deinduction) of a VEGF-sequestering soluble receptor, we show that VEGF is indispensable for adjusting the coronary vasculature to match increased oxygen consumption and exploit this finding to generate a hypoperfused heart. Importantly, ensuing ischemia is tunable to a level at which large cohorts of cardiomyocytes are driven to enter a hibernation mode, without cardiac cell death. Relieving the VEGF blockade even months later resulted in rapid revascularization and full recovery of contractile function. Furthermore, we show that left ventricular remodeling associated with hibernation is also fully reversible. The unique opportunity to uncouple hibernation from other ischemic heart phenotypes (e.g., infarction) was used to determine the genetic program of hibernation; uncovering hypoxia-inducible factor target genes associated with metabolic adjustments and induced expression of several cardioprotective genes. Autophagy, specifically self-digestion of mitochondria, was identified as a key prosurvival mechanism in hibernating cardiomyocytes. This system may lend itself for examining the potential utility of treatments to rescue dysfunctional cardiomyocytes and reverse maladaptive remodeling.

Right atrial thrombi are related to indwelling central venous catheter position: Insights into time course and possible mechanism of formation

We studied the effect of central line catheters on thrombus formation in the right atrium (RA), including the incidence and echocardiographic characteristics of the catheter-associated thrombus as well as possible clinical implications in patients. We prospectively studied 55 patients by transesophageal echocardiography within 1 week after Hickman catheter implantation and on a follow-up study at 6 to 8 weeks. We succeeded in imaging the catheter tip in 48 of the 55 patients (87%). In the baseline study 13 had the tip placed in the RA, eight at the superior vena cava-atrium junction, and 27 in the superior vena cava. An abnormal mass, consistent with a thrombus, was found in 12.5% of the patients, all of which were seen within the 13-patient (46%) group with the Hickman catheter tip placed in the RA. Hickman catheter insertion is associated with high incidence (12.5%) of early formation of RA thrombus. The formation of these thrombi is asymptomatic and highly associated (p < 0.001) with the catheter tip position in the RA, in contrast to their positioning in the superior vena cava or in its junction with the right atrium. On the basis of these findings, we recommend that special attention and effort be given to placing of the catheter tip in the superior vena cava and avoiding the RA during the implantation procedure.

Effect of three-dimensional valve shape on the hemodynamics of aortic stenosis: Three-dimensional echocardiographic stereolithography and patient studies

OBJECTIVES This study tested the hypothesis that the impact of a stenotic aortic valve depends not only on the cross-sectional area of its limiting orifice but also on three-dimensional (3D) valve geometry. BACKGROUND Valve shape can potentially affect the hemodynamic impact of aortic stenosis by altering the ratio of effective to anatomic orifice area (the coefficient of orifice contraction [Cc]). For a given flow rate and anatomic area, a lower Cc increases velocity and pressure gradient. This effect has been recognized in mitral stenosis but assumed to be absent in aortic stenosis (constant Cc of 1 in the Gorlin equation). METHODS In order to study this effect with actual valve shapes in patients, 3D echocardiography was used to reconstruct a typical spectrum of stenotic aortic valve geometrics from doming to flat. Three different shapes were reproduced as actual models by stereolithography (computerized laser polymerization) with orifice areas of 0.5, 0.75, and 1.0 cm(2) (total of nine valves) and studied with physiologic flows. To determine whether valve shape actually influences hemodynamics in the clinical setting, we also related Cc (= continuity/planimeter areas) to stenotic aortic valve shape in 35 patients with high-quality echocardiograms. RESULTS In the patient-derived 3D models, Cc varied prominently with valve shape, and was largest for long, tapered domes that allow more gradual flow convergence compared with more steeply converging flat valves (0.85 to 0.90 vs. 0.71 to 0.76). These variations translated into differences of up to 40% in pressure drop for the same anatomic area and flow rate, with corresponding variations in Gorlin (effective) area relative to anatomic values. In patients, Cc was significantly lower for flat versus doming bicuspid valves (0.73 +/- 0.14 vs. 0.94 +/- 0.14, p < 0.0001) with 40 +/- 5% higher gradients (p < 0.0001). CONCLUSIONS Three-dimensional valve shape is an important determinant of pressure loss in patients with aortic stenosis, with smaller effective areas and higher pressure gradients for flatter valves. This effect can translate into clinically important differences between planimeter and effective valve areas (continuity or Gorlin). Therefore, valve shape provides additional information beyond the planimeter orifice area in determining the impact of valvular aortic stenosis on patient hemodynamics.

Restricted diastolic opening of the mitral leaflets in patients with left ventricular dysfunction: evidence for increased valve tethering

OBJECTIVES We tested the hypothesis that patients with incomplete systolic mitral leaflet closure (IMLC: apically displaced coaptation) also have restricted diastolic leaflet opening that is independent of mitral inflow volume and provides evidence supporting increased leaflet tethering. BACKGROUND Competing hypotheses for functional mitral regurgitation (MR) with IMLC include global left ventricular (LV) dysfunction per se (reduced leaflet closing force) versus geometric distortion of the mitral apparatus by LV dilation (augmented leaflet tethering). These are inseparable in systole, but restricted leaflet motion has also been observed in diastole, and attributed to reduced mitral inflow. METHODS Diastolic mitral leaflet excursion and orifice area were measured by two-dimensional echocardiography in 58 patients with global LV dysfunction, 36 with and 22 without IMLC, compared with 21 normal subjects. The biplane Simpsons method was used to calculate LV ejection volume, which equals mitral inflow volume in the absence of aortic regurgitation. RESULTS The diastolic mitral leaflet excursion angle was markedly reduced in patients with IMLC compared with those without IMLC, whose ventricles were smaller, and normal subjects (17 +/- 10 degrees vs. 58 +/- 13 degrees vs. 67 +/- 8 degrees, p < 0.0001). Excursion angle was dissociated from mitral inflow volume (r2 = 0.04); excursion was reduced in patients with IMLC despite a normal inflow volume in the larger ventricles with MR (60 +/- 25 vs. 61 +/- 12 ml in normal subjects, p = NS), and excursion was nearly normal in patients without IMLC despite reduced inflow volume (40 +/- 10 ml, p < 0.001 vs. normal subjects). The anterior leaflet when maximally open coincided well with the line connecting its attachments to the anterior annulus and papillary muscle tip (angular difference = 3 +/- 7 degrees vs. 25 +/- 9 degrees vs. 32 +/- 10 degrees in patients with and without IMLC vs. normal subjects, p < 0.0001). In patients with IMLC, the leaflet tip orifice was smaller in an anteroposterior direction but wider than in the other groups, giving a normal total area (6.8 +/- 1.8 vs. 7.1 +/- 1.2 vs. 6.9 +/- 0.8 cm2, p = NS). CONCLUSIONS Patients with LV dysfunction and systolic IMLC also have restricted diastolic leaflet excursion that is independent of inflow volume, coincides with the tethering line connecting the annulus and papillary muscle and reflects limitation of anterior motion relative to the posteriorly placed papillary muscles without a decrease in total orifice area. These observations are consistent with increased tethering by displaced mitral leaflet attachments in the dilated ventricles of patients with IMLC that can restrict both diastolic opening and systolic closure.

Troponin elevation in severe sepsis and septic shock: The role of left ventricular diastolic dysfunction and right ventricular dilatation

Objective:Serum troponin concentrations predict mortality in almost every clinical setting they have been examined, including sepsis. However, the causes for troponin elevations in sepsis are poorly understood. We hypothesized that detailed investigation of myocardial dysfunction by echocardiography can provide insight into the possible causes of troponin elevation and its association with mortality in sepsis. Design:Prospective, analytic cohort study. Setting:Tertiary academic institute. Patients:A cohort of ICU patients with severe sepsis or septic shock. Interventions:Advanced echocardiography using global strain, strain-rate imaging and 3D left and right ventricular volume analyses in addition to the standard echocardiography, and concomitant high-sensitivity troponin-T measurement in patients with severe sepsis or septic shock. Measurements and Main Results:Two hundred twenty-five echocardiograms and concomitant high-sensitivity troponin-T measurements were performed in a cohort of 106 patients within the first days of severe sepsis or septic shock (2.1 ± 1.4 measurements/patient). Combining echocardiographic and clinical variables, left ventricular diastolic dysfunction defined as increased mitral E-to-strain-rate e′-wave ratio, right ventricular dilatation (increased right ventricular end-systolic volume index), high Acute Physiology and Chronic Health Evaluation-II score, and low glomerular filtration rate best correlated with elevated log-transformed concomitant high-sensitivity troponin-T concentrations (mixed linear model: t = 3.8, 3.3, 2.8, and –2.1 and p = 0.001, 0.0002, 0.006, and 0.007, respectively). Left ventricular systolic dysfunction determined by reduced strain-rate s′-wave or low ejection fraction did not significantly correlate with log(concomitant high-sensitivity troponin-T). Forty-one patients (39%) died in-hospital. Right ventricular end-systolic volume index and left ventricular strain-rate e′-wave predicted in-hospital mortality, independent of Acute Physiology and Chronic Health Evaluation-II score (logistic regression: Wald = 8.4, 6.6, and 9.8 and p = 0.004, 0.010, and 0.001, respectively). Concomitant high-sensitivity troponin-T predicted mortality in univariate analysis (Wald = 8.4; p = 0.004), but not when combined with right ventricular end-systolic volume index and strain-rate e′-wave in the multivariate analysis (Wald = 2.3, 4.6, and 6.2 and p = 0.13, 0.032, and 0.012, respectively). Conclusions:Left ventricular diastolic dysfunction and right ventricular dilatation are the echocardiographic variables correlating best with concomitant high-sensitivity troponin-T concentrations. Left ventricular diastolic and right ventricular systolic dysfunction seem to explain the association of troponin with mortality in severe sepsis and septic shock.

Acute Aortic Intramural Hematoma: An Analysis From the International Registry of Acute Aortic Dissection

Background— Acute aortic intramural hematoma (IMH) is an important subgroup of aortic dissection, and controversy surrounds appropriate management. Methods and Results— Patients with acute aortic syndromes in the International Registry of Acute Aortic Dissection (1996–2011) were evaluated to examine differences between patients (based on the initial imaging test) with IMH or classic dissection (AD). Of 2830 patients, 178 had IMH (64 type A [42%], 90 type B [58%], and 24 arch). Patients with IMH were older and presented with similar symptoms, such as severe pain. Patients with type A IMH were less likely to present with aortic regurgitation or pulse deficits and were more likely to have periaortic hematoma and pericardial effusion. Although type A IMH and AD were managed medically infrequently, type B IMH were more frequently treated medically. Overall in-hospital mortality was not statistically different for type A IMH compared to AD (26.6% versus 26.5%; P=0.998); type A IMH managed medically had significant mortality (40.0%), although less than classic AD (61.8%; P=0.195). Patients with type B IMH had a hospital mortality that was less but did not differ significantly (4.4% versus 11.1%; P=0.062) from classic AD. One-year mortality was not significantly different between AD and IMH. Conclusions— Acute IMH has similar presentation to classic AD but is more frequently complicated with pericardial effusions and periaortic hematoma. Patients with IMH have a mortality that does not differ statistically from those with classic AD. A small subgroup of type A IMH patients are managed medically and have a significant in-hospital mortality.