Barbara M. Richartz

Gender-Related Differences in Acute Aortic Dissection

Background—Few data exist on gender-related differences in clinical presentation, diagnostic findings, management, and outcomes in acute aortic dissection (AAD). Methods and Results—Accordingly, we evaluated 1078 patients enrolled in the International Registry of Acute Aortic Dissection (IRAD) to assess differences in clinical features, management, and in-hospital outcomes between men and women. Of the patients enrolled in IRAD (32.1%) with AAD, 346 were women. Although less frequently affected by AAD (32.1% of AAD), women were significantly older and had more often presented later than men (P =0.008); symptoms of coma/altered mental status were more common, whereas pulse deficit was less common. Diagnostic imaging suggestive of rupture, ie, periaortic hematoma, and pleural or pericardial effusion were more commonly observed in women. In-hospital complications of hypotension and tamponade occurred with greater frequency in women, resulting in higher in-hospital mortality compared with men. After adjustment for age and hypertension, women with aortic dissection die more frequently than men (OR, 1.4, P =0.04), predominantly in the 66- to 75-year age group. Moreover, surgical outcome was worse in women than men (P =0.013); type A dissection in women was associated with a higher surgical mortality of 32% versus 22% in men despite similar delay, surgical technique, and hemodynamics. Conclusions—Our analysis provides insights into gender-related differences in AAD with regard to clinical characteristics, management, and outcomes; important diagnostic and therapeutic implications may help shed light on aortic dissection in women to improve their outcomes.

Angiographic Assessment of Collateral Connections in Comparison With Invasively Determined Collateral Function in Chronic Coronary Occlusions

Background—The evaluation of new therapeutic modalities to induce collateral growth in coronary artery disease require improved methods of angiographic characterization of collaterals, which should be validated by quantitative assessment of collateral function. Methods and Results—In 100 patients with total chronic occlusion of a major coronary artery (duration >2 weeks) collaterals were assessed angiographically by the Rentrop grading, by their anatomic location, and by a new grading of collateral connections (CC grade 0: no continuous connection, CC1: threadlike continuous connection, CC2: side branch–like connection). The interobserver variability was 10%. Collateral function was assessed by Doppler flow (average peak velocity) and pressure recordings distal to the occlusion before recanalization. A collateral resistance index (RColl) was calculated. Recruitable collateral flow was measured during a final balloon inflation >30 minutes after the baseline measurement. The comparison of the anatomic location, the Rentrop, and the collateral connection grade showed only for the latter an independent and significant relation with RColl. CC2 collaterals preserved regional left ventricular function better than did CC1 collaterals and provided a higher collateral flow reserve during adenosine infusion. CC0 collaterals were predominantly observed in recent occlusions of 2 to 4 weeks’ duration, with the highest RColl. During balloon reocclusion, recruitable collateral function was best preserved with CC2 and least with CC0. Conclusions—The angiographic grading of collateral connections in total chronic occlusions could differentiate collaterals according to their functional capacity to preserve regional left ventricular function and was closely associated with invasively determined parameters of collateral hemodynamics.

Prolonged QTc Interval and High B-Type Natriuretic Peptide Levels Together Predict Mortality in Patients With Advanced Heart Failure

Background—The role of QTc interval prolongation in heart failure remains poorly defined. To better understand it, we analyzed the QTc interval duration in patients with heart failure with high B-type natriuretic peptide (BNP) levels and analyzed the combined prognostic impact of prolonged QTc and elevated BNP. Methods and Results—QTc intervals were measured in 241 patients with heart failure who had BNP levels >400 pg/mL. QT interval duration was determined by averaging 3 consecutive beats through leads II and V4 on a standard 12-lead ECG and corrected by using the Bazett formula. QTc intervals were prolonged (>440 ms) in 122 (51%) patients and normal in 119 (49%). The BNP levels in these 2 groups were not significantly different (786±321 pg/mL in the prolonged QTc group versus 733±274 pg/mL in the normal QTc group, P =0.13). During 6 months of follow-up, 46 patients died, 9 underwent transplantation, and 17 underwent left ventricular assist device implantation. The deaths were attributed to pump failure (n=24, 52%), sudden cardiac death (n=18, 39%), or noncardiac causes (n=4, 9%). Kaplan-Meier survival rates were 3 times higher in the normal QTc group than in the prolonged QTc group (P <0.0001). On multivariate analysis, prolonged QTc interval was an independent predictor of all-cause death (P =0.0001), cardiac death (P =0.0001), sudden cardiac death (P =0.004), and pump failure death (P =0.0006). Conclusions—Prolonged QTc interval is a strong, independent predictor of adverse outcome in patients with heart failure with BNP levels >400 pg/mL.

Immediate Changes of Collateral Function After Successful Recanalization of Chronic Total Coronary Occlusions

Background—Coronary collaterals are essential to maintain myocardial function in chronic total coronary occlusions (TCOs). The aim of the present study was to assess the collateral circulation in TCOs before coronary angioplasty and to determine the recruitable collateral perfusion after recanalization by use of intracoronary Doppler flow velocimetry. Methods and Results—In 21 patients with TCOs (duration >4 weeks), Doppler recordings of basal collateral flow were obtained before the first balloon inflation. Angioplasty was performed with stent implantation in all lesions. At the end of the procedure, recruitable collateral flow was measured during a repeat balloon inflation. The collateral flow index (CFI) was calculated from the velocity integral during the occlusion/velocity integral of antegrade flow. In 17 of 21 patients, angiography was repeated after 24 hours, and CFI was reassessed. Average peak velocity of collateral flow was 10.9±5.6 cm/s with a predominantly systolic flow (diastolic/systolic velocity ratio <0.5) compared with antegrade flow (diastolic/systolic velocity ratio >1.5). After recanalization, the average peak velocity of recruitable collateral flow dropped by >50% to 4.7±2.5 cm/s. CFI fell from 0.48±0.25 to 0.21±0.16 (P <0.001). There was no further change of CFI during the following 24 hours. CFI was higher in patients with preserved regional ventricular function than in those with akinetic myocardium (0.57±0.23 versus 0.38±0.12, P <0.05). Conclusions—Collateral circulation in TCO provided 50% of antegrade coronary flow. A considerable fraction of collateral flow was immediately lost after recanalization, indicating that TCO may not remain protected from future ischemic events by a well-developed collateral function.

Safety, Efficacy, and Indications of β-Adrenergic Receptor Blockade to Reduce Heart Rate prior to Coronary CT Angiography

For selected indications, coronary computed tomographic (CT) angiography is an established clinical technology for evaluation in patients suspected of having or known to have coronary artery disease. In coronary CT angiography, image quality is highly dependent on heart rate, with heart rate reduction to less than 60 beats per minute being important for both image quality and radiation dose reduction, especially when single-source CT scanners are used. β-Blockers are the first-line option for short-term reduction of heart rate prior to coronary CT angiography. In recent years, multiple β-blocker administration protocols with oral and/or intravenous application have been proposed. This review article provides an overview of the indications, efficacy, and safety of β-blockade protocols prior to coronary CT angiography with respect to different scanner techniques. Moreover, implications for radiation exposure and left ventricular function analysis are discussed.

Aortic intramural haematoma: natural history and predictive factors for complications

Intramural haematoma (IMH) of the aorta is attracting growing interest as a variant of aortic dissection and is more frequently diagnosed by modern tomographic imaging modalities in the evaluation of acute aortic syndromes.1,2 The evolution from IMH to overt dissection or even rupture may occur suddenly or is heralded by ongoing acute aortic (pain) syndrome. Unlike classic aortic dissection, IMH has no mechanisms of decompression by a re-entry tear but rather reveals intramural (intramedial) thickening or echolucent pockets of non-communicating blood with potential for rupture or, at times, regression and resorption of haematoma with time.3–6 As in overt dissection, widening of the mediastinum or the aortic shadow, pleural effusion and pain, aortic regurgitation, and pericardial effusion may emerge after initial IMH, whereas focal neurological signs or malperfusion syndrome are incidental.7 Hence, the subtle initial pathology of IMH is more likely to be missed than overt dissection, especially in the absence of recurrent pain (“aortic syndrome”). While diagnostic and therapeutic implications of IMH continue to impact on vascular medicine, description of natural course and prediction of individual risk is far from settled.6,8–10 Observational data from independent groups revealed evidence that the IMH evolves to resorption or progression to either classic dissection, contained rupture or formation of an aneurysm within 30 days of hospital admission. Proximal location of IMH is clearly considered an independent predictor of progression to dissection, contained rupture, or aneurysm formation. In our series of 66 cases of IMH (38 type A and 28 type B), 73% of progressive IMH were type A as compared to 44% in stable IMH (odds ratio (OR) 4.3, 95% confidence interval (CI) 1.5 to 12.3; p  =  0.02); early progression was unrelated to age, sex, chronic arterial hypertension, Marfan syndrome, bicuspid aortic valve, and both …

Impaired acute collateral recruitment as a possible mechanism for increased cardiac adverse events in patients with diabetes mellitus

BACKGROUND The mortality of coronary artery disease is increased in diabetic patients. An impaired collateral function is considered a possible explanation. This study should assess the influence of diabetes on collaterals by direct invasive assessment of collateral function. METHODS In 90 consecutive patients with a chronic coronary occlusion (TCO) of >2 weeks duration a recanalization was done. Thirty patients with diabetes (33%) were compared with 60 (67%) without diabetes. Blood flow velocity and pressure were measured distal to the occlusion by intracoronary Doppler and pressure wires before PTCA, and again after PTCA during a final balloon reocclusion to assess acute recruitment of collaterals. Resistance indexes for collaterals (R(Coll)) and peripheral microcirculation (R(P)) were calculated. RESULTS The R(Coll)(diabetics: 8.1+/-6.8 vs nondiabetics: 8.7+/-6.7 mmHg cm(-1)s(-1); p=0.68) and R(P)(5.6+/-4.2 vs 6.6+/-3.8 mmHg cm(-1)s(-1); p=0.30) were similar in diabetic and nondiabetic patients before recanalization. During balloon reocclusion both R(Coll)and R(P)increased. This increase was significantly more pronounced in diabetic than in nondiabetic patients in TCOs <3 months duration. In TCOs of longer duration (> or =3 months) these differences were no longer detectable between both patient groups. CONCLUSIONS Diabetic patients with TCOs have similarly developed collaterals as nondiabetic patients. However, in TCOs <3 months duration the acute recruitment of collaterals in case of reocclusion is impaired. This could explain some of the higher complication rate and mortality after coronary interventions in diabetic patients.

Reversibility of coronary endothelial vasomotor dysfunction in idiopathic dilated cardiomyopathy: acute effects of vitamin C

In patients with idiopathic dilated cardiomyopathy, endothelium vasomotor function is disturbed. Increased oxidative stress and the consecutive formation of oxygen free radicals have been implicated as one possibility for this observation, suggesting that nitric oxide (NO) is inactivated by oxygen free radicals. We tested the hypothesis that the antioxidant, vitamin C, may improve endothelial function in idiopathic dilated cardiomyopathy. In 11 patients, the endothelium-dependent vasomotor response of the left anterior descending coronary artery to intracoronary acetylcholine (ACh) infusion (1/2 x 10(-6) mol/L, 1/4 x 10(-5) mol/L; respectively) was determined before and immediately after intravenous infusion of 3 g of vitamin C. Coronary cross-sectional diameter was obtained by quantitative coronary angiography, average peak velocity was measured by an intracoronary Doppler flow wire, and coronary blood flow (CBF) was calculated. Maximum cross-sectional diameter was determined after administration of nitroglycerin. Dose-dependent ACh showed a decrease in cross-sectional diameter (-5% to -7%, p <0.05) and an increase in average peak velocity (+16% to +25%, p <0.05); the CBF was unchanged (+1% to -2%, p = NS). After vitamin C infusion, the cross-sectional diameter increased in a dose-dependent manner from +11% to +15%, the average peak velocity increased from +20% to + 41% (p <0.05), and the CBF increased from +38% to + 82% (p <0.01, p <0.001, respectively). Thus, patients with idiopathic dilated cardiomyopathy had endothelial dysfunction, and administration of vitamin C reversed endothelium-dependent dysfunction.

Comparison of left ventricular systolic and diastolic function in patients with idiopathic dilated cardiomyopathy and mild heart failure versus those with severe heart failure

The pathogenesis of acute pulmonary edema in idiopathic dilated cardiomyopathy (IDC) is not completely understood. Because pulse-wave tissue Doppler imaging (TDI) allows a direct comparison between systolic as well as diastolic wall motion velocities, we tested the hypothesis that acute pulmonary edema is caused by both systolic and diastolic failure. We prospectively studied 65 patients. Forty patients had IDC (group 1), 15 of whom had recent-onset pulmonary congestion (group 1a, New York Heart Association [NYHA] functional classes III and IV) and 25 of whom were in clinically stable condition without signs of pulmonary congestion (group 1b, NYHA I and II). All of these patients were restudied after 3, 7, and 45 days. Groups 1a and 1b were compared with 25 subjects without evidence of heart disease (group 2). Peak systolic wall motion velocity (Vs), peak wall motion velocity of the early (Ve), and late (Va) filling waves were measured by TDI; mitral inflow pattern was determined by pulse-wave Doppler and left ventricular (LV) ejection fraction (EF) by 2-dimensional echocardiography. In those patients without pulmonary edema (controls and group 1b, n = 50), we found a positive correlation between LVEF and Vs (r = 0.72, p <0.001) and between LVEF and Ve (r = 0.79, p <0.001). Early diastolic wall motion velocity always exceeded peak systolic wall motion velocity (Ve/Vs ratio >1). In patients with IDC with recent-onset pulmonary congestion (group 1a), Ve was significantly lower compared with group 1b (3.5 +/- 0.2 vs 4.9 +/- 0.4 cm/s, p <0.01, Ve/Vs ratio <1). Clinical improvement was paralled by a gradual increase in Ve (3.5 +/- 0.2 to 6.8 +/- 0.3 cm/s, p <0.01) but not in Vs or LVEF. Thus, in patients with IDC acute pulmonary edema is exclusively caused by diastolic rather than systolic failure.

Turbulent flow as a cause for underestimating coronary flow reserve measured by Doppler guide wire

BackgroundDoppler-tipped coronary guide-wires (FW) are well-established tools in interventional cardiology to quantitatively analyze coronary blood flow. Doppler wires are used to measure the coronary flow velocity reserve (CFVR). The CFVR remains reduced in some patients despite anatomically successful coronary angioplasty. It was the aim of our study to test the influence of changes in flow profile on the validity of intra-coronary Doppler flow velocity measurements in vitro. It is still unclear whether turbulent flow in coronary arteries is of importance for physiologic studies in vivo.MethodsWe perfused glass pipes of defined inner diameters (1.5 – 5.5 mm) with heparinized blood in a pulsatile flow model. Laminar and turbulent flow profiles were achieved by varying the flow velocity. The average peak velocity (APV) was recorded using 0.014 inch FW. Flow velocity measurements were also performed in 75 patients during coronary angiography. Coronary hyperemia was induced by intra-coronary injection of adenosine. The APV maximum was taken for further analysis. The mean luminal diameter of the coronary artery at the region of flow velocity measurement was calculated by quantitative angiography in two orthogonal planes.ResultsIn vitro, the measured APV multiplied with the luminal area revealed a significant correlation to the given perfusion volumes in all diameters under laminar flow conditions (r2 > 0.85). Above a critical Reynolds number of 500 – indicating turbulent flow – the volume calculation derived by FW velocity measurement underestimated the actual rate of perfusion by up to 22.5 % (13 ± 4.6 %). In vivo, the hyperemic APV was measured irrespectively of the inherent deviation towards lower velocities. In 15 of 75 patients (20%) the maximum APV exceeded the velocity of the critical Reynolds number determined by the in vitro experiments.ConclusionDoppler guide wires are a valid tool for exact measurement of coronary flow velocity below a critical Reynolds number of 500. Reaching a coronary flow velocity above the velocity of the critical Reynolds number may result in an underestimation of the CFVR caused by turbulent flow. This underestimation of the flow velocity may reach up to 22.5 % compared to the actual volumetric flow. Cardiologists should consider this phenomena in at least 20 % of patients when measuring CFVR for clinical decision making.