Sorajja, Paul

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 cm 2 ) and preserved ejection fraction (≥50%) using 2-dimensional and Doppler echocardiography. Patients were stratified by stroke volume index (<35 mL/m 2 [low flow, LF] versus ≥35 mL/m 2 [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.

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 cm 2 ) 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/m 2 ). 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 cm 2 ; 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.

Background— The pathophysiology of low flow, low gradient severe aortic stenosis (LGSAS) with preserved ejection fraction is poorly understood. It has been proposed that abnormalities of arterial circulation are a major contributor to this syndrome. Methods and Results— We invasively examined systemic arterial afterload (effective arterial elastance, Ea; total arterial compliance, Ca; and systemic vascular resistance index) in patients with LGSAS (mean gradient, <40 mm Hg; aortic valve area, <1.0 cm 2 ) and preserved ejection fraction (≥50%), and compared these findings with patients with high gradient (≥40 mm Hg) severe aortic stenosis (HGSAS) and moderate AS (mean gradient, <40 mm Hg; aortic valve area, >1.0 cm 2 ). Patients with LGSAS (n=36), HGSAS (n=31), and moderate AS (n=19) were similar with respect to age, sex, body size, symptoms, comorbidities, and ejection fraction. Aortic valve area was similar between groups with LGSAS and HGSAS, but the patients with LGSAS had reduced stroke volume index and cardiac index ( P =0.003 for both). In comparison with patients with HGSAS and moderate AS, measures of afterload, including Ea (4.02±0.98 versus 3.13±0.81 and 3.06±0.79 mm Hg·m 2 /mL; P <0.0001) and systemic vascular resistance index (3116±799 versus 2515±645 and 2380±546 dyn·s·m 2 /cm 5 ; P =0.001), were significantly higher in LGSAS, whereas Ca was lower (0.46±0.16 versus 0.57±0.13 and 0.59±0.19 mL/m 2 per mm Hg; P =0.002). All invasive measures of arterial afterload were related to stroke volume index. Conclusions— Patients with LGSAS and preserved ejection fraction display elevated arterial afterload compared with patients with HGSAS and moderate AS. These findings identify systemic arterial effects that contribute to the hemodynamic presentation in patients with LGSAS and help to further define this entity.

Background— High sensitivity C-reactive protein (hsCRP) has been identified as a predictor of adverse cardiovascular outcomes. Whether hsCRP is a useful biomarker for risk stratification in contemporary percutaneous coronary intervention remains unknown. Methods and Results— We conducted a prospective study among 513 patients undergoing non-emergency percutaneous coronary intervention and examined the relationship between pre- and postprocedural hsCRP levels and outcomes. The patients were divided according to the median preprocedural hsCRP level (0.3 mg/dL). Patients with high hsCRP had significantly more adverse clinical characteristics. Preprocedural hsCRP level was an independent predictor of periprocedural myocardial infarction (odds ratio per doubling of hsCRP 1.15 [95% confidence interval, 1.01–1.31]; P =0.038). Unadjusted mortality (29.7% versus 9.9%; P <0.001) and the combined end point of death or myocardial infarction (36.5% versus 16.0%, P <0.001) during a follow-up of 5 years were markedly greater in patients with high preprocedural hsCRP. Similar relationships existed for postprocedural hsCRP. However, after multivariable adjustment, neither preprocedural hsCRP levels (hazard ratio per doubling 0.96 [0.92, 1.00]; P =0.066) nor postprocedural hsCRP levels (hazard ratio 0.98 [0.94, 1.02]; P =0.27) were significantly associated with mortality. Conclusions— High hsCRP is associated with a greater independent risk of periprocedural myocardial infarction, as defined by the universal definition, but is not an independent determinant of mortality after percutaneous coronary intervention. Our findings suggest that routine measurement of hsCRP in patients undergoing percutaneous coronary intervention in contemporary practice is unlikely to be beneficial.

Percutaneous coronary interventions (PCI) may be performed during the same session as diagnostic catheterization (ad hoc PCI) or at a later session (delayed PCI). Randomized trials comparing these strategies have not been performed; cohort studies have not identified consistent differences in safety or efficacy between the two strategies. Ad hoc PCI has increased in prevalence over the past decade and is the default strategy for treating acute coronary syndromes. However, questions about its appropriateness for some patients with stable symptoms have been raised by the results of recent large trials comparing PCI to medical therapy or bypass surgery. Ad hoc PCI for stable ischemic heart disease requires preprocedural planning, and reassessment after diagnostic angiography must be performed to ensure its appropriateness. Patients may prefer ad hoc PCI because it is convenient. Payers may prefer ad hoc PCI because it is cost‐efficient. The majority of data confirm equivalent outcomes in ad hoc versus delayed PCI. However, there are some situations in which delayed PCI may be safer or yield better outcomes. This document reviews patient subsets and clinical situations in which one strategy is preferable over the other. © 2012 Wiley Periodicals, Inc.

Background— The clinical efficacy of alcohol septal ablation for obstructive hypertrophic cardiomyopathy (HCM) has been demonstrated, but the long-term effects of the procedure remain uncertain. This study examined the survival of patients after septal ablation performed in a tertiary HCM referral center. Methods and Results— We examined 177 patients (mean age, 64 years; 68% women) who underwent septal ablation at our institution. Over a follow-up of 5.7 years, survival free of all mortality was no different than the expected survival for a comparable general population, and similar to that of age- and sex-matched patients who underwent isolated surgical myectomy (8-year survival estimate, 79% versus 79%; P =0.64). For the end point of documented sudden cardiac death or unknown cause of death, the incidence per 100 person-year follow-up was 1.31 (95% confidence interval, 0.60–2.38). Residual left ventricular outflow tract gradient after ablation was an independent predictor of long-term survival free of any death. Conclusions— In this nonrandomized study of carefully selected patients undergoing septal ablation by experienced operators in a tertiary referral HCM center, long-term survival was favorable and similar to that of an age- and sex-matched general population, and to patients undergoing surgical myectomy, as well, without an increased risk of sudden cardiac death.