Zachary M. Gertz

Predictors of mortality and outcomes of therapy in low-flow severe aortic stenosis a placement of aortic transcatheter Valves (PARTNER) trial analysis

Background— The prognosis and treatment of patients with low-flow (LF) severe aortic stenosis are controversial. Methods and Results— The Placement of Aortic Transcatheter Valves (PARTNER) trial randomized patients with severe aortic stenosis to medical management versus transcatheter aortic valve replacement (TAVR; inoperable cohort) and surgical aortic valve replacement versus TAVR (high-risk cohort). Among 971 patients with evaluable echocardiograms (92%), LF (stroke volume index ⩽35 mL/m2) was observed in 530 (55%); LF and low ejection fraction (<50%) in 225 (23%); and LF, low ejection fraction, and low mean gradient (<40 mm Hg) in 147 (15%). Two-year mortality was significantly higher in patients with LF compared with those with normal stroke volume index (47% versus 34%; hazard ratio, 1.5; 95% confidence interval, 1.25–1.89; P=0.006). In the inoperable cohort, patients with LF had higher mortality than those with normal flow, but both groups improved with TAVR (46% versus 76% with LF and 38% versus 53% with normal flow; P<0.001). In the high-risk cohort, there was no difference between TAVR and surgical aortic valve replacement. In patients with paradoxical LF and low gradient (preserved ejection fraction), TAVR reduced 1-year mortality from 66% to 35% (hazard ratio, 0.38; P=0.02). LF was an independent predictor of mortality in all patient cohorts (hazard ratio, ≈1.5), whereas ejection fraction and gradient were not. Conclusions— LF is common in severe aortic stenosis and independently predicts mortality. Survival is improved with TAVR compared with medical management and similar with TAVR and surgical aortic valve replacement. A measure of flow (stroke volume index) should be included in the evaluation and therapeutic decision making of patients with severe aortic stenosis. Clinical Trial Registration— URL: http://www.clinicaltrial.gov. Unique identifier: NCT0053089.4.

Predictors of Mortality and Outcomes of Therapy in Low Flow Severe Aortic Stenosis: A PARTNER Trial Analysis

Background— The prognosis and treatment of patients with low-flow (LF) severe aortic stenosis are controversial. Methods and Results— The Placement of Aortic Transcatheter Valves (PARTNER) trial randomized patients with severe aortic stenosis to medical management versus transcatheter aortic valve replacement (TAVR; inoperable cohort) and surgical aortic valve replacement versus TAVR (high-risk cohort). Among 971 patients with evaluable echocardiograms (92%), LF (stroke volume index ⩽35 mL/m2) was observed in 530 (55%); LF and low ejection fraction (<50%) in 225 (23%); and LF, low ejection fraction, and low mean gradient (<40 mm Hg) in 147 (15%). Two-year mortality was significantly higher in patients with LF compared with those with normal stroke volume index (47% versus 34%; hazard ratio, 1.5; 95% confidence interval, 1.25–1.89; P=0.006). In the inoperable cohort, patients with LF had higher mortality than those with normal flow, but both groups improved with TAVR (46% versus 76% with LF and 38% versus 53% with normal flow; P<0.001). In the high-risk cohort, there was no difference between TAVR and surgical aortic valve replacement. In patients with paradoxical LF and low gradient (preserved ejection fraction), TAVR reduced 1-year mortality from 66% to 35% (hazard ratio, 0.38; P=0.02). LF was an independent predictor of mortality in all patient cohorts (hazard ratio, ≈1.5), whereas ejection fraction and gradient were not. Conclusions— LF is common in severe aortic stenosis and independently predicts mortality. Survival is improved with TAVR compared with medical management and similar with TAVR and surgical aortic valve replacement. A measure of flow (stroke volume index) should be included in the evaluation and therapeutic decision making of patients with severe aortic stenosis. Clinical Trial Registration— URL: http://www.clinicaltrial.gov. Unique identifier: NCT0053089.4.

Marked changes in right ventricular contractile pattern after cardiothoracic surgery: Implications for post-surgical assessment of right ventricular function

BACKGROUND Longitudinal shortening accounts for the majority of right ventricular (RV) contraction in normal hearts. This finding accounts for the correlation between longitudinal measures of RV contraction such as tricuspid annular plane systolic excursion (TAPSE) and global RV function. We hypothesized that, after cardiac surgery, there are major differences in the RV contractile pattern relative to normal hearts. METHODS We retrospectively studied 2 cardiac surgical cohorts who underwent cardiopulmonary bypass (CPB) with pericardial incision (OHT, n = 54; CABG, n = 23) and compared them with a lung transplant cohort (n = 25). We compared TAPSE, RV fractional area change (RVFAC) and relative change in RV transverse and longitudinal area in the surgical cohorts with data from normal subjects (n = 84). RESULTS RVFAC was lower in the surgical groups compared with the normal group, yet still in the normal range (37% to 42% vs 47%; p < 0.01). TAPSE was markedly lower in OHT (15 ± 3 mm) and CABG (16 ± 4 mm) than in normal (26 ± 4 mm) subjects (p < 0.01), as was the relative contribution of longitudinal area change (OHT group 51 ± 11%, CABG group 54 ± 13%, normal group 78 ± 14%; p < 0.01). The ratio of TAPSE to RVFAC was markedly lower in CABG (40 ± 14 mm/%FAC) and OHT (37 ± 10 mm/%FAC) patients than in normal (56 ± 14 mm/%FAC) subjects (p < 0.001). However, OLT patients had a higher TAPSE (18 ± 3 mm) than OHT (15 ± 3 mm) and CABG (16 ± 4 mm) patients (p < 0.01) and a higher relative contribution of longitudinal area change: OLT 67 ± 10%; OHT 51 ± 11%; and CABG 54 ± 13% (p < 0.01). CONCLUSIONS After cardiac surgery, the RV contractile pattern changes, with a relative loss of longitudinal shortening and gain in transverse shortening despite normal global RV function. These findings have major implications for quantitative assessment of RV function after cardiac surgery, suggesting that global measures of RV function assessment may be preferred in this setting and that lower normative ranges should be used when measurement of RV function is performed with longitudinal methods.

Site-Specific Atherogenic Gene Expression Correlates With Subsequent Variable Lesion Development in Coronary and Peripheral Vasculature

Objectives—The relationship between specific gene regulation and subsequent development and progression of atherosclerosis is incompletely understood. We hypothesized that genes in the vasculature related to cholesterol metabolism, inflammation, and insulin signaling pathways are differentially regulated in a site-specific and time-dependent manner. Methods and Results—Expression of 59 genes obtained from coronary, carotid, and thoracic aortic arteries were characterized from diabetic (DM)/hypercholesterolemic (HC) swine (n=52) 1, 3, and 6 months after induction. Lesion development in the 3 arterial beds was quantified and characterized at 1, 3, 6, and 9 months. Progressive lesion development was observed in the coronary>thoracic aorta≫carotid arteries. Genes involved in cholesterol metabolism and insulin pathways were upregulated in coronaries>thoracic aortae>carotids. Inflammatory genes were more markedly upregulated in coronary arteries than the other 2 arteries. Genes implicated in plaque instability (eg, matrix metalloproteinase-9, CCL2 and Lp-PLA2 mRNAs) were only upregulated at 6 months in coronary arteries. Conclusions—Variable gene expression, both in regard to the arterial bed and duration of disease, was associated with variable plaque development and progression. These findings may provide further insight into the atherosclerotic process and development of potential therapeutic targets.

Effects of Atrial Fibrillation on Treatment of Mitral Regurgitation in the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) Randomized Trial

OBJECTIVES The purpose of this study was to characterize patients with mitral regurgitation (MR) and atrial fibrillation (AF) treated percutaneously using the MitraClip device (Abbott Vascular, Abbott Park, Illinois) and compare the results with surgery in this population. BACKGROUND The EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) randomized controlled trial compared a less invasive catheter-based treatment for MR with surgery, providing an opportunity to assess the impact of AF on the outcomes of both the MitraClip procedure and surgical repair. METHODS The study population included 264 patients with moderately severe or severe MR assessed by an independent echocardiographic core laboratory. Comparison of safety and effectiveness study endpoints at 30 days and 1 year were made using both intention-to-treat and per-protocol (cohort of patients with MR ≤2+ at discharge) analyses. RESULTS Pre-existing AF was present in 27% of patients. These patients were older, had more advanced disease, and were more likely to have a functional etiology. Similar reduction of MR to ≤2+ before discharge was achieved in patients with AF (83%) and in patients without AF (75%, p = 0.3). Freedom from death, mitral valve surgery for valve dysfunction, and MR >2+ was similar at 12 months for AF patients (64%) and for no-AF patients (61%, p = 0.3). At 12 months, MR reduction to <2+ was greater with surgery than with MitraClip, but there was no interaction between rhythm and MR reduction, and no difference in all-cause mortality between patients with and patients without AF. CONCLUSIONS Atrial fibrillation is associated with more advanced valvular disease and noncardiac comorbidities. However, acute procedural success, safety, and 1-year efficacy with MitraClip therapy is similar for patients with AF and without AF.

Intracoronary delivery of bone-marrow-derived stem cells

Ischemic heart disease is the single greatest killer of Americans and its complications are a major cause of congestive heart failure and ventricular arrhythmias while signifiicantly contributing to increased health care costs and reduced patient quality of life. Advances in medical therapy, although signifiicant over the past decade, are still inadequate in regards to targeting the prime underlying pathology, the irreversible loss of damaged or dead cardiomyocytes. Research into the use of cell transplantation therapy to treat cardiac diseases, with the goal of improving cardiac function, shows promise. The aim of this review will be to discuss the potential therapeutic effects of myocardial stem cell and progenitor cell therapy delivered by an intracoronary route with special reference to treatment of infarcted myocardium.

The impact of mitral regurgitation on patients undergoing catheter ablation of atrial fibrillation.

AIMS Mitral regurgitation (MR) causes left atrium (LA) enlargement and subsequent atrial fibrillation (AF). The presence of MR may increase recurrence rates after AF ablation. The purpose of this study was to determine the impact of MR on recurrence rates after catheter ablation of AF. METHODS AND RESULTS We compared 95 patients with moderate or greater baseline MR (defined by MR jet area to LA area ratio ≥ 0.2) and AF undergoing ablation to 95 randomly selected patients without significant MR undergoing AF ablation. Electrocardiographic recurrence at 1-year follow-up was the primary outcome. Patients in the MR cohort had mean MR/LA ratio 0.37 vs. 0.09 in controls (P< 0.0001). Mitral regurgitation patients had larger LA dimension (4.5 vs. 4.1 cm, P< 0.0001) and more persistent AF (71 vs. 28%, P< 0.0001). Mitral regurgitation patients had higher recurrence rates than controls (61 vs. 46%, P= 0.04). The degree of MR was higher in patients with recurrence (MR/LA ratio 0.25 vs. 0.20, P= 0.03), as was LA dimension (4.5 vs. 4.1 cm, P< 0.0001). In multivariate analyses, only LA size was an independent predictor of recurrence (odds ratio 2.9 per centimetre increase in LA dimension, P= 0.005). Fifty-five percent of MR patients had normal leaflet motion, with MR likely due to atrial remodelling secondary to AF. CONCLUSION Mitral regurgitation was associated with increased AF recurrence after AF ablation, but its impact was mediated by LA size. Left atrium size was the only independent predictor of AF recurrence. The high percentage of MR that was likely secondary to AF may have impacted our findings and deserves further study.

Comparison of Invasive and Noninvasive Assessment of Aortic Stenosis Severity in the Elderly

Background— Aortic valve area (AVA) in aortic stenosis (AS) can be assessed noninvasively or invasively, typically with similar results. These techniques have not been validated in elderly patients, where common assumptions make them most prone to error. Accurate assessment of AVA is crucial to determine which patients are appropriate candidates for aortic valve replacement. Methods and Results— Fifty elderly patients (mean 86 years, 46% female) referred for cardiac catheterization to evaluate AS also underwent transthoracic echocardiography within 24 hours. To minimize assumptions all patients had 3-dimensional echocardiography (Echo-3D), and at catheterization using directly measured oxygen consumption (Cath-mVo2) and thermodilution cardiac output (Cath-TD). Correlation between Cath-mVo2 and Echo-3D AVA was poor (r=0.41). Cath-TD AVA had a moderate correlation with Echo-3D AVA (r=0.59). Cath-mVo2 (AVA=0.69 cm2) and Cath-TD (AVA=0.66 cm2) underestimated AVA compared with Echo-3D (AVA=0.76 cm2; P=0.08 for comparison with Cath-mVo2; P=0.001 for Cath-TD). Compared with Echo-3D, the sensitivity and specificity for determining critical disease (AVA <0.8 cm2) were 81% and 42% for Cath-mVo2, and 97% and 53% for Cath-TD. The only independent predictor of the difference between noninvasive and invasive AVA was stroke volume index (P<0.01). Resistance, a less flow-dependent measure, showed a stronger correlation between Echo-3D and Cath-mVo2 (r=0.69), and Echo-3D and Cath-TD (r=0.77). Conclusions— Standard techniques of AVA assessment for AS show poor correlation in elderly patients, with frequent misclassification of critical AS. Less flow-dependent measures, such as resistance, should be considered to ensure that only appropriate patients are treated with aortic valve replacement.

Local Drug Delivery for Treatment of Coronary and Peripheral Artery Disease

Local drug delivery (LDD), the direct application of a therapeutic agent to a focal location, has been used in cardiovascular interventions to prophylactically reduce neointimal hyperplasia and relieve clot burden. LDD allows targeted use of drugs whose toxicities inhibit their systemic use while stent delivery allows for consistent and prolonged delivery. Stents eluting limus family drugs or paclitaxel inhibit vascular smooth muscle cell hyperplasia and migration and clinical use of such stents have reduced restenosis rates after percutaneous coronary procedures. However, associated with the increased efficacy is an increased rate of late stent thrombosis associated with death and myocardial infarction. Recent innovations, including bioabsorbable polymers and completely bioabsorbable stents may expand the use of drug-eluting stents. In this review, we discuss the development, the clinical use, and the effects of LDD from balloon and stent-based platforms in the treatment of restenosis and thrombus.

Application of appropriate use criteria to cardiac stress testing in the hospital setting: limitations of the criteria and areas for improved practice.

Imaging cardiac stress test use has risen significantly, leading to the development of appropriate use criteria. Prior studies have suggested the rate of inappropriate testing is 13% to 14%, but inappropriate testing in hospitalized patients has not been well studied.