Mackram F. Eleid

Flow-Gradient Patterns in Severe Aortic Stenosis With Preserved Ejection Fraction Clinical Characteristics and Predictors of Survival

Background— Among patients with severe aortic stenosis (AS) and preserved ejection fraction, those with low gradient (LG) and reduced stroke volume may have an adverse prognosis. We investigated the prognostic impact of stroke volume using the recently proposed flow-gradient classification. Methods and Results— We examined 1704 consecutive patients with severe AS (aortic valve area <1.0 cm2) and preserved ejection fraction (≥50%) using 2-dimensional and Doppler echocardiography. Patients were stratified by stroke volume index (<35 mL/m2 [low flow, LF] versus ≥35 mL/m2 [normal flow, NF]) and aortic gradient (<40 mm Hg [LG] versus ≥40 mm Hg [high gradient, HG]) into 4 groups: NF/HG, NF/LG, LF/HG, and LF/LG. NF/LG (n=352, 21%), was associated with favorable survival with medical management (2-year estimate, 82% versus 67% in NF/HG; P<0.0001). LF/LG severe AS (n=53, 3%) was characterized by lower ejection fraction, more prevalent atrial fibrillation and heart failure, reduced arterial compliance, and reduced survival (2-year estimate, 60% versus 82% in NF/HG; P<0.001). In multivariable analysis, the LF/LG pattern was the strongest predictor of mortality (hazard ratio, 3.26; 95% confidence interval, 1.71–6.22; P<0.001 versus NF/LG). Aortic valve replacement was associated with a 69% mortality reduction (hazard ratio, 0.31; 95% confidence interval, 0.25–0.39; P<0.0001) in LF/LG and NF/HG, with no survival benefit associated with aortic valve replacement in NF/LG and LF/HG. Conclusions— NF/LG severe AS with preserved ejection fraction exhibits favorable survival with medical management, and the impact of aortic valve replacement on survival was neutral. LF/LG severe AS is characterized by a high prevalence of atrial fibrillation, heart failure, and reduced survival, and aortic valve replacement was associated with improved survival. These findings have implications for the evaluation and subsequent management of AS severity.

Spontaneous Coronary Artery Dissection Revascularization Versus Conservative Therapy

Background—Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic acute coronary syndrome for which optimal management remains undefined. Methods and Results—We performed a retrospective study of 189 patients presenting with a first SCAD episode. We evaluated outcomes according to initial management: (1) revascularization versus conservative therapy and (2) percutaneous coronary intervention (PCI) versus conservative therapy stratified by vessel flow at presentation. Demographics were similar in revascularization versus conservative (mean age, 44±9 years; women 92% both groups), but vessel occlusion was more frequent in revascularization (44/95 versus 18/94). There was 1 in-hospital death (revascularization) and 1 late death (conservative). Procedural failure rate was 53% in those managed with PCI. In the subgroup of patients presenting with preserved vessel flow, rates of PCI failure were similarly high (50%), and 6 (13%) required emergency coronary artery bypass grafting. In the conservative group, 85 of 94 (90%) had an uneventful in-hospital course, but 9 (10%) experienced early SCAD progression requiring revascularization. Kaplan–Meier estimated 5-year rates of target vessel revascularization and recurrent SCAD were no different in revascularization versus conservative therapy (30% versus 19%; P=0.06 and 23% versus 31%; P=0.7). Conclusions—PCI for SCAD is associated with high rates of technical failure even in those presenting with preserved vessel flow and does not protect against target vessel revascularization or recurrent SCAD. A strategy of conservative management with prolonged observation may be preferable.

Coronary Artery Tortuosity in Spontaneous Coronary Artery Dissection Angiographic Characteristics and Clinical Implications

Background—Spontaneous coronary artery dissection (SCAD) is an increasingly recognized nonatherosclerotic cause of acute coronary syndrome. The angiographic characteristics of SCAD are largely undetermined. The goal of this study was to determine the prevalence of coronary tortuosity in SCAD and whether it may be implicated in the disease. Methods and Results—Patients with confirmed SCAD (n=246; 45.3±8.9 years; 96% women) and 313 control patients without SCAD or coronary artery disease who underwent coronary angiography were included in this case–control study. Angiograms were reviewed for coronary tortuosity and assigned a tortuosity score. Tortuosity was common in patients presenting with their first SCAD event (78% versus 17% in controls; P<0.0001; tortuosity score, 4.41±1.73 versus 2.33±1.49 in controls; P<0.0001) despite a low prevalence of hypertension (34%). Recurrent SCAD (n=40) occurred within segments of tortuosity in 80% of cases. Severe tortuosity (≥2 consecutive curvatures ≥180°) was associated with a higher risk of recurrent SCAD (hazard ratio, 3.29; 95% confidence interval, 0.99–8.29; P=0.05). Tortuosity score >5 was associated with a trend toward higher risk of recurrent SCAD (P=0.16). Prespecified angiographic markers of tortuosity including corkscrew appearance and multivessel symmetrical tortuosity were associated with extracoronary vasculopathy including fibromuscular dysplasia (P<0.05 for both). Conclusions—Coronary artery tortuosity is highly prevalent in the SCAD population and is associated with recurrent SCAD. Recurrent SCAD most often occurs within segments of tortuosity. Angiographic features of SCAD are associated with extracoronary vasculopathy, including fibromuscular dysplasia. These findings suggest that coronary tortuosity may serve as a marker or potential mechanism for SCAD.

Carotid Intima-Media Thickness and Coronary Artery Calcium Score as Indications of Subclinical Atherosclerosis

OBJECTIVE To determine the ability of carotid intima-media thickness (CIMT) and coronary artery calcium score (CACS) to detect subclinical atherosclerosis in a young to middle-aged, low-risk, primary-prevention population. PATIENTS AND METHODS Patients aged 36 to 59 years who underwent determination of CIMT and CACS at our institution between May 1, 2004, and April 1, 2008, were included in the study. Those with diabetes mellitus or a history of coronary, peripheral, or cerebral vascular disease were excluded. Other information, such as Framingham risk score (FRS), was obtained by a review of clinical and laboratory data. RESULTS Of 118 patients, 89 (75%) had a CACS of zero and 94 (80%) were men; mean ± SD age was 48.9±5.7 years. The mean FRS of this group was 4.0; 86 patients (97%) were considered at low risk ( CONCLUSION Subclinical vascular disease can be detected by CIMT evaluation in young to middle-aged patients with a low FRS and a CACS of zero. These findings have important implications for vascular disease screening and the implementation of primary-prevention strategies.

Preoperative Dobutamine Stress Echocardiographic Findings and Subsequent Short-Term Adverse Cardiac Events After Orthotopic Liver Transplantation

Cardiovascular (CV) complications are the leading cause of non–graft‐related death in orthotopic liver transplant (OLT) patients. Pretransplant cardiac evaluation using dobutamine stress echocardiography (DSE) is commonly utilized for risk stratification of OLT candidates. To determine if clinical and echocardiographic variables identify patients with increased CV risk, we performed a retrospective chart review of all 284 patients that underwent OLT at our institution between June 1999 and August 2005. Of these patients, 157 had a DSE prior to their OLT. Serious adverse CV events occurring during surgery and up to 4 months post‐transplantation were defined as cardiac‐related death, myocardial infarction (MI), new heart failure, or asystole or unstable ventricular arrhythmia requiring acute treatment. Sixteen of 157 patients (10%) had an adverse CV event with 2 deaths. These included ventricular tachycardia (n = 8), asystole (n = 2), MI (n = 5), and new heart failure (n = 1). Nine of the 16 CV events occurred at the time of surgery (including both deaths), 5 occurred postoperatively, and 3 occurred after hospital discharge. Variables that correlated with increased CV events were inability during DSE to achieve >82% of the maximum predicted heart rate (22% versus 6%, P = 0.01), a peak rate pressure product during DSE of <16,333 (17% versus 5%, P = 0.02), and a Model for End‐Stage Liver Disease (MELD) score of >24 at the time of OLT. A multivariate model calculated from the DSE maximum achieved heart rate (MAHR) and MELD score (result = 3.78 + 0.07 MELD − 0.05 MAHR) identified a 47% risk for a value > 0 versus a 6% risk for a value < 0 (P < 0.001). In conclusion, the maximum heart rate achieved during DSE together with the MELD score may be a predictor of adverse CV events up to 4 months post‐OLT. A large prospective study is needed to more decisively support this conclusion. Liver Transpl 14:886–892, 2008.

Systemic Hypertension in Low Gradient Severe Aortic Stenosis with Preserved Ejection Fraction

Background— Low-gradient severe aortic stenosis with preserved ejection fraction is an increasingly recognized entity, and symptomatic patients may benefit from aortic valve replacement. However, systemic hypertension frequently coexists with low-gradient severe aortic stenosis, which itself may cause elevated left ventricular (LV) filling pressures with resultant symptoms of dyspnea. Methods and Results— Symptomatic patients with hypertension (aortic systolic pressure >140 mm Hg) and low-gradient (mean gradient <40 mm Hg) severe aortic stenosis (aortic valve area <1 cm2) with preserved ejection fraction (ejection fraction >50%) who underwent invasive hemodynamic catheterization of the left and right sides of the heart received infusion of intravenous sodium nitroprusside to reduce blood pressure and arterial afterload. At baseline, patients had severe hypertension (aortic systolic pressure, 176±26 mm Hg), pulmonary hypertension (mean pressure, 39±12 mm Hg), elevated LV end-diastolic pressure (19±5 mm Hg), and reduced stroke volume (33±8 mL/m2). All measures of afterload were reduced with nitroprusside (P<0.001 for all). Nitroprusside reduced mean pulmonary artery pressure (25±10 mm Hg) and LV end-diastolic pressure (11±5 mm Hg; P<0.001 for both compared with baseline). Aortic valve area (0.86±0.11 to 1.02±0.16 cm2; P=0.001) and mean gradient (27±5 to 29±6 mm Hg; P=0.02) increased with nitroprusside. Conclusions— Systemic hypertension in low-gradient severe aortic stenosis with preserved ejection fraction is associated with elevated LV filling pressures and pulmonary hypertension. Treatment of hypertension with vasodilator therapy results in a lowering of the total LV afterload, with a decrease in LV filling pressures and pulmonary artery pressures. These findings have important implications for the management of patients with low-gradient severe aortic stenosis with preserved ejection fraction and hypertension.

Inconsistent echocardiographic grading of aortic stenosis: is the left ventricular outflow tract important?

Objective Discrepancy in the echocardiographic severity grading of aortic stenosis (AS) based on current guidelines has been reported. We sought to investigate the left ventricular outflow tract diameter (LVOTd) as a source of inconsistencies, and to explore hypothetical alternatives for discrepancy improvement. Design Retrospective echocardiographic cross-sectional analysis. Setting From 2000 to 2010, we identified all AS patients with left ventricular EF ≥50%, mean gradient (MG) ≥20 mm Hg, aortic valve area (AVA) ≤2.5 cm2, <moderate (2+) aortic regurgitation; and divided them into three groups: patients with ‘small ’ LVOTd 1.7–1.9 cm, ‘average’ LVOTd 2.0–2.2 cm and ‘large’ LVOTd ≥2.3 cm. In each group, inconsistency of data for classification of severity of AS was assessed and alternative thresholds explored. Results Of 9488 total patients, 58% were men, LVOTd 2.18±0.19 cm, peak velocity (Vmax) 3.9±0.8 m/s, MG 37±16 mm Hg, and AVA 1.09±0.34 cm2. Small LVOTd patients were older women (91%) with worse systemic haemodynamics and more prevalent paradoxical low-flow, compared with average and large LVOTd patients (all parameters p <0.001). Despite clinically similar MG and Vmax across all groups, mean AVA ranged from 0.88 to 1.25 cm2 (p <0.001), classifying small LVOTd patients as severe, average LVOTd as moderate-severe and large LVOTd as moderate. For patients with large, average and small LVOTd, an AVA of 1 cm2 corresponded to MG of 42, 35 and 29 mm Hg, Vmax of 4.1, 3.8 and 3.5 m/s and dimensionless index (DI) of 0.22, 0.29 and 0.36, respectively. An AVA cut-off of 0.8 cm2 reduced severe AS inconsistency from 48% to 26% for small LVOTd patients. An AVA cut-off of 0.9 cm2 reduced severe AS inconsistency from 37% to 26% for average LVOTd patients. The current AVA cut-off of 1 cm2 was consistent for large LVOTd patients. Conclusions The LVOTd is associated with significant inconsistencies in AS assessment by current guidelines. For patients with normal EF and normal flow, current guideline definition of severe AS is most consistent for patients with large LVOTd, but not so for patients with average or small LVOTd in whom lower AVA cut-offs should be further studied. The DI cut-off for severe AS is highly variable depending on the LVOTd and guideline revision of this threshold should be considered.

Mitral valve disease—current management and future challenges

The field of mitral valve disease diagnosis and management is rapidly changing. New understanding of disease pathology and progression, with improvements in and increased use of sophisticated imaging modalities, have led to early diagnosis and complex treatment. In primary mitral regurgitation, surgical repair is the standard of care. Treatment of asymptomatic patients with severe mitral regurgitation in valve reference centres, in which successful repair is more than 95% and surgical mortality is less than 1%, should be the expectation for the next 5 years. Transcatheter mitral valve repair with a MitraClip device is also producing good outcomes in patients with primary mitral regurgitation who are at high surgical risk. Findings from clinical trials of MitraClip versus surgery in patients of intermediate surgical risk are expected to be initiated in the next few years. In patients with secondary mitral regurgitation, mainly a disease of the left ventricle, the vision for the next 5 years is not nearly as clear. Outcomes from ongoing clinical trials will greatly inform this field. Use of transcatheter techniques, both repair and replacement, is expected to substantially expand. Mitral annular calcification is an increasing problem in elderly people, causing both mitral stenosis and regurgitation which are difficult to treat. There is anecdotal experience with use of transcatheter valves by either a catheter-based approach or as a hybrid technique with open surgery, which is being studied in early feasibility trials.

Natural history of left ventricular mechanics in transplanted hearts: relationships with clinical variables and genetic expression profiles of allograft rejection.

OBJECTIVES The aim of this study was to explore the temporal evolution of left ventricular (LV) mechanics in relation to clinical variables and genetic expression profiles implicated in cardiac allograft function. BACKGROUND Considerable uncertainty exists regarding the range and determinants of variability in LV systolic performance in transplanted hearts (TXH). METHODS Fifty-one patients (mean age 53 ± 12 years; 37 men) underwent serial assessment of echocardiograms, cardiac catheterization, gene expression profiles, and endomyocardial biopsy data within 2 weeks and at 3, 6, 12, and 24 months after transplantation. Two-dimensional speckle-tracking data were compared between patients with TXH and 37 controls (including 12 post-coronary artery bypass patients). Post-transplantation mortality and hospitalizations were recorded with a median follow-up period of 944 days. RESULTS Global longitudinal strain (LS) and radial strain remained attenuated in patients with TXH at all time points (p < 0.001 and p = 0.005), independent of clinical rejection episodes. Failure to improve global LS at 3 months (≥ 1 SD) was associated with higher incidence of death and cardiac events (hazard ratio: 5.92; 95% confidence interval: 1.96 to 17.91; p = 0.049). Multivariate analysis revealed gene expression score as the only independent predictor of global LS (R(2) = 0.53, p = 0.005), with SEMA7A gene expression having the highest correlation with global LS (r = -0.84, p < 0.001). CONCLUSIONS Speckle tracking-derived LV strains are helpful in estimating the burden of LV dysfunction in patients with TXH that evolves independent of biopsy-detected cellular rejection. Failure to improve global LS at 3 months after transplantation is associated with a higher incidence of death and cardiac events. Serial changes in LV mechanics correlate with peripheral blood gene expression profiles and may affect the clinical assessment of long-term prognosis in patients with TXH.

Type A aortic dissection in patients with bicuspid aortic valves: clinical and pathological comparison with tricuspid aortic valves

Objective Bicuspid aortic valve (BAV) is associated with a higher risk of type A aortic dissection (AD) compared with tricuspid aortic valve (TAV). We sought to study differences between patients with BAV and TAV with AD. Design and setting Observational descriptive analysis of clinical, imaging and pathological characteristics of all patients with confirmed BAV and AD from 1980–2010, compared with a consecutive TAV group with AD. Results Of 47 patients with BAV (mean age 58±14, 77% male), 31 (66%) had acute AD, 16 (34%) had chronic AD, 40 (85%) had typical BAV, 32 (68%) had hypertension and 11 (23%) had previous aortic coarctation repair. Of 53 patients with TAV (mean age 66±13 (p=0.007), 76% male), 34 (66%) had acute AD (p=1.0) and 46 (87%) had hypertension (p=0.03). More patients with BAV had known aortic dilatation prior to AD (49% versus 17%, p=0.001). Presentation symptoms were identical between groups (p=NS). Maximal ascending aortic diameter at AD was higher in patients with BAV (66±15 mm vs 56±11 mm, p=0.0004). Previous aortic valve replacement (AVR) was more common in BAV (23% vs 6%, p=0.02). Of 11 patients with BAV with previous isolated AVR, 7 had ≥moderate ascending aorta dilatation at the time of surgery. Patients with BAV had increased aortic jet velocity (28% vs 10%) and more severe aortic stenosis (19% vs 0%) at presentation (p=0.04 and 0.002, respectively). In acute AD, aortic medial degeneration affected 75% of BAV specimens and 41% TAV specimens (p=0.01) while aortic atherosclerosis was more frequent in TAV (56% vs 26%, p=0.02). Conclusions Compared with patients with TAV, patients with BAV with type A AD are younger, have less hypertension, more valve stenosis and previous AVR, higher maximal aortic dimension, worse aortic medial degeneration, high prevalence of aortic coarctation, and 1 out of 2 have known aortic dilatation prior to AD. Implementation of current guidelines could have theoretically prevented AD in several patients with BAV.