Sachin S. Goel

Severe Aortic Stenosis and Coronary Artery Disease—Implications for Management in the Transcatheter Aortic Valve Replacement Era : A Comprehensive Review

Management of coronary artery disease (CAD) in patients with severe aortic stenosis (AS) referred for transcatheter aortic valve replacement (TAVR) is posing challenges. Due to limited and heterogeneous data on the prevalence and clinical impact of CAD on the outcomes of TAVR and the management strategies for CAD in patients undergoing TAVR, we performed a comprehensive review of the literature. Significant CAD is present in 40% to 75% of patients undergoing TAVR. The impact of CAD on outcomes after TAVR remains understudied. Based on existing data, not all patients require revascularization before TAVR. Percutaneous coronary intervention (PCI) should be considered for severely stenotic lesions in proximal coronaries that subtend a large area of myocardium at risk. Ongoing studies randomizing patients to surgical or percutaneous management strategies for severe AS will help provide valuable data regarding the impact of CAD on TAVR outcomes, the role of PCI, and its timing in relation to TAVR.

Characterization and outcome of patients with severe symptomatic aortic stenosis referred for percutaneous aortic valve replacement

OBJECTIVE Many high-risk patients with severe symptomatic aortic stenosis are not referred for surgical aortic valve replacement. Although this patient population remains ill-defined, many of these patients are now being referred for percutaneous aortic valve replacement. We sought to define the characteristics and outcomes of patients referred for percutaneous aortic valve replacement. METHODS Between February 2006 and March 2007, 92 patients were screened for percutaneous aortic valve replacement. Clinical and echocardiographic characteristics of patients undergoing surgical aortic valve replacement, percutaneous aortic valve replacement, balloon aortic valvuloplasty, or no intervention were compared. The primary end point was all-cause mortality. RESULTS Nineteen patients underwent successful surgical aortic valve replacement, 18 patients underwent percutaneous aortic valve replacement, and 36 patients had no intervention. Thirty patients underwent balloon aortic valvuloplasty, and of these, 8 patients were bridged to percutaneous aortic valve replacement and 3 were bridged to surgical aortic valve replacement. Of the remaining 19 patients undergoing balloon aortic valvuloplasty, bridging to percutaneous aortic valve replacement could not be accomplished because of death (n = 9 [47%)], exclusion from the percutaneous aortic valve replacement protocol (n = 6 [32%]), and some patients improved after balloon aortic valvuloplasty and declined percutaneous aortic valve replacement (n = 4 [21%]). The most common reasons for no intervention included death while awaiting definitive treatment (n = 10 [28%]), patient uninterested in percutaneous aortic valve replacement (n = 10 [28%]), and questionable severity of symptoms or aortic stenosis (n = 9 [25%]). Patients not undergoing aortic valve replacement had higher mortality compared with those undergoing aortic valve replacement (44% vs 14%) over a mean duration of 220 days. CONCLUSION Symptomatic patients with severe aortic stenosis have high mortality if timely aortic valve replacement is not feasible. Twenty percent of the patients referred for percutaneous aortic valve replacement underwent surgical aortic valve replacement with good outcome. Patients undergoing balloon aortic valvuloplasty alone or no intervention had unfavorable outcomes.

Prevalence and outcomes of unoperated patients with severe symptomatic mitral regurgitation and heart failure: comprehensive analysis to determine the potential role of MitraClip for this unmet need.

To the Editor: Mitral valve (MV) surgery is recommended in patients with severe symptomatic mitral regurgitation (MR) [(1)][1]. The role of MV surgery is unclear in patients with severe MR secondary to left ventricular (LV) dysfunction [(1)][1]. Many patients with severe MR are at high surgical

Percutaneous coronary intervention in patients with severe aortic stenosis: implications for transcatheter aortic valve replacement.

Background— With the availability of transcatheter aortic valve replacement, management of coronary artery disease in patients with severe aortic stenosis (AS) is posing challenges. Outcomes of percutaneous coronary intervention (PCI) in patients with severe AS and coronary artery disease remain unknown. We sought to compare the short-term outcomes of PCI in patients with and without AS. Methods and Results— From our PCI database, we identified 254 patients with severe AS who underwent PCI between 1998 and 2008. Using propensity matching, we found 508 patients without AS who underwent PCI in the same period. The primary end point of 30-day mortality after PCI was similar in patients with and without severe AS (4.3% [11 of 254] versus 4.7% [24 of 508]; hazard ratio, 0.93; 95% confidence interval, 0.51–1.69; P=0.2). Patients with low ejection fraction (⩽30%) and severe AS had a higher 30-day post-PCI mortality compared with those with an ejection fraction >30% (5.4% [7 of 45] versus 1.2% [4 of 209]; P<0.001). In addition, AS patients with high Society of Thoracic Surgeons score (≥10) had a higher 30-day post-PCI mortality than those with a Society of Thoracic Surgeons score <10 (10.4% [10 of 96] versus 0%; P<0.001). Conclusions— PCI can be performed in patients with severe symptomatic AS and coronary artery disease without an increased risk of short-term mortality compared with propensity-matched patients without AS. Patients with ejection fraction ⩽30% and Society of Thoracic Surgeons score ≥10% are at a highest risk of 30-day mortality after PCI. This finding has significant implications in the management of severe coronary artery disease in high-risk severe symptomatic AS patients being considered for transcatheter aortic valve replacement.Background— With the availability of transcatheter aortic valve replacement, management of coronary artery disease in patients with severe aortic stenosis (AS) is posing challenges. Outcomes of percutaneous coronary intervention (PCI) in patients with severe AS and coronary artery disease remain unknown. We sought to compare the short-term outcomes of PCI in patients with and without AS. Methods and Results— From our PCI database, we identified 254 patients with severe AS who underwent PCI between 1998 and 2008. Using propensity matching, we found 508 patients without AS who underwent PCI in the same period. The primary end point of 30-day mortality after PCI was similar in patients with and without severe AS (4.3% [11 of 254] versus 4.7% [24 of 508]; hazard ratio, 0.93; 95% confidence interval, 0.51–1.69; P =0.2). Patients with low ejection fraction (≤30%) and severe AS had a higher 30-day post-PCI mortality compared with those with an ejection fraction >30% (5.4% [7 of 45] versus 1.2% [4 of 209]; P <0.001). In addition, AS patients with high Society of Thoracic Surgeons score (≥10) had a higher 30-day post-PCI mortality than those with a Society of Thoracic Surgeons score <10 (10.4% [10 of 96] versus 0%; P <0.001). Conclusions— PCI can be performed in patients with severe symptomatic AS and coronary artery disease without an increased risk of short-term mortality compared with propensity-matched patients without AS. Patients with ejection fraction ≤30% and Society of Thoracic Surgeons score ≥10% are at a highest risk of 30-day mortality after PCI. This finding has significant implications in the management of severe coronary artery disease in high-risk severe symptomatic AS patients being considered for transcatheter aortic valve replacement. # Clinical Perspective {#article-title-29}

Prognostic implications of pulmonary hypertension in patients with severe aortic stenosis

OBJECTIVE We sought to determine the clinical outcomes of patients undergoing surgical aortic valve replacement with hemodynamically confirmed severe pulmonary hypertension and aortic stenosis and compare them with the outcomes of patients not undergoing aortic valve replacement and patients undergoing aortic valve replacement with mild-to-moderate pulmonary hypertension. METHODS A total of 317 patients with severe aortic stenosis (aortic valve area < 1 cm(2)) underwent right heart catheterization along with left heart catheterization between 2004 and 2009. Severe pulmonary hypertension (mean pulmonary artery pressure > 35 mm Hg) was present in 81 patients, of whom 35 (43.2%) underwent surgical aortic valve replacement. We compared the clinical outcomes of these 35 patients with the 46 patients with severe pulmonary hypertension who did not undergo surgical aortic valve replacement. RESULTS Thirty-day mortality after aortic valve replacement was 2.85% in patients with severe pulmonary hypertension and 10.86% in patients not undergoing aortic valve replacement (P = .001). During a mean follow-up of 339.0 ± 343.7 days, overall mortality in patients undergoing aortic valve replacement was 14.2% in patients with severe pulmonary hypertension and 50% in patients with severe pulmonary hypertension who did not undergo aortic valve replacement (P < .0001). On the other hand, among patients who underwent surgery, overall mortality was similar in both the mild-to-moderate pulmonary hypertension group (23 patients [20.3%]) and the severe pulmonary hypertension group at the end of the follow-up period (P = .4). In a multivariate analysis, the presence of chronic obstructive pulmonary disease and the lack of reduction in mean pulmonary artery pressure were independent predictors of mortality in these high-risk patients undergoing aortic valve replacement, whereas baseline mean pulmonary artery pressure was not a predictor. Preoperative pulmonary capillary wedge pressure was a significant predictor of postoperative reduction in mean pulmonary artery pressure. CONCLUSIONS In patients with severe aortic stenosis and severe pulmonary hypertension who undergo aortic valve replacement, baseline pulmonary artery pressure does not unfavorably affect survival. Aortic valve replacement should be considered for patients with aortic stenosis with severe pulmonary hypertension, especially with higher pulmonary capillary wedge pressure.

Lessons Learned from Balloon Aortic Valvuloplasty Experience from the Pre-transcatheter Aortic Valve Implantation Era

BACKGROUND Balloon aortic valvuloplasty (BAV) has been used as a bridge to surgical aortic valve replacement (SAVR) in high-risk patients with severe symptomatic aortic stenosis (AS). Such patients are now being referred for transcatheter aortic valve implantation (TAVI). We sought to study the indications and outcomes of BAV in patients with severe AS in the pre-TAVI era. METHODS We analyzed consecutive patients with severe AS undergoing BAV from 1990 to 2005. In these patients with no immediate surgical option, BAV was attempted to temporarily improve hemodynamics, with a goal to improve general health of the patient, and ultimately AVR. RESULTS A total of 99 BAVs (eight repeats, one second repeat) were performed in 90 consecutive patients. Baseline ejection fraction was ≤25% in 36 (36%) patients. The 30-day mortality rate was 17% (n = 17). Of the 99 patients, 27 (30%) underwent AVR. Average follow-up of patients with and without AVR was 55 ± 57 months and 16 ± 23 months, respectively. The 6-month and 1-year survival rates in patients who underwent AVR were 81% and 78%, respectively, versus 57% and 44% in patients who did not undergo AVR (P = 0.024). CONCLUSION BAV can be used successfully to clinically improve the health of some nonsurgical patients with severe symptomatic AS, and a proportion of these patients improve to a point where AVR can be performed. Bridging to TAVI will provide further options to high-risk patients who cannot be bridged to conventional AVR. The role of BAV in bridging to TAVI merits further study.

Do Bisphosphonates Slow the Progression of Aortic Stenosis

OBJECTIVES The aim of this study was to investigate the impact of bisphosphonates on the progression of aortic stenosis. BACKGROUND Valvular calcification is associated with the development and progression of aortic stenosis. Bisphosphonates have been suggested to slow this progression. METHODS Female patients older than the age of 60 years with an aortic valve area (AVA) between 1.0 and 2.0 cm(2) were identified and studied retrospectively. Only those who had follow-up echocardiograms at least a year apart were included. Primary outcomes were the change in AVA and valvular gradients over time. Mortality and freedom from aortic valve replacement were also studied. A propensity-matching method was applied for the probability of the use of bisphosphonates. RESULTS The study included 801 female patients (mean age, 76 ± 7.6 years) with a mean follow-up of 5.1 ± 2.4 years. The mean duration of bisphosphonate use was 3.1 ± 2.6 years. At the time of the initial echocardiogram, 323 patients (38%) were taking bisphosphonates. The mean ejection fraction at baseline was 56.7 ± 9.6% with a mean AVA of 1.32 ± 0.25 cm(2). Peak and mean gradients were 28.4 ± 11 mm Hg and 15.6 ± 6.8 mm Hg, respectively. Propensity matching was successfully performed for 438 patients. On follow-up, there were no differences in the rate of change in AVA or peak and mean gradients when patients were stratified based on the use of bisphosphonates. Bisphosphonates also had no impact on survival or freedom from aortic valve replacement. CONCLUSIONS In this retrospective analysis of older female patients, bisphosphonates do not have a significant impact on the hemodynamic or clinical progression of aortic stenosis.

Stent Thrombosis With Second-Generation Drug-Eluting Stents Compared With Bare-Metal Stents Network Meta-Analysis of Primary Percutaneous Coronary Intervention Trials in ST-Segment–Elevation Myocardial Infarction

Background—The relative safety of drug-eluting stents (DESs) and bare-metal stents (BMSs) with respect to stent thrombosis (ST) continues to be debated. There are limited data comparing safety and efficacy of second-generation DES to BMS. We compared the clinical outcomes between second-generation DES and BMS for primary percutaneous coronary intervention using network meta-analysis. Methods and Results—Randomized controlled trials comparing stent types (first-generation DES, second-generation DES or BMS) were considered for inclusion. A search strategy used Medline, Embase, Cochrane databases, and proceedings of the international meetings. Information about study design, inclusion criteria, and sample characteristics were extracted. Network meta-analysis was used to pool direct (comparison of second-generation DES to BMS) and indirect evidence (first-generation DES with BMS and second-generation DES) from the randomized trials. Twenty-one trials comparing all stents types, including 12 866 patients randomly assigned to treatment groups, were analyzed. A significantly lower incidence of ST was noted with the use of second-generation DES as early as 30 days (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.15–0.82) and between 31 days and 1 year (OR, 0.49; 95% CI, 0.30–0.79) when compared with BMS. Second-generation DES was associated with significantly lower incidence of definite ST at 1 year (OR, 0.3; 95% CI, 0.11–0.83) and myocardial infarction (OR, 0.3; 95% CI, 0.17–0.54) and target vessel revascularization at 1 year (OR, 0.54; 95% CI, 0.80–0.98) when compared with BMS. There was no difference in mortality at 30 days (OR, 0.84; 95% CI, 0.45–1.59) or 1 year (OR, 0.80; 95% CI, 0.56–1.14) with the use of second-generation DES versus BMS. The small number of events may influence the precision of the analysis. Conclusions—Network meta-analysis of randomized trials of primary percutaneous coronary intervention demonstrated lower incidence of ST, myocardial infarction, and target vessel revascularization with second-generation DES when compared with BMS. The use of second-generation DES for percutaneous coronary intervention in ST-segment–elevation myocardial infarction was not associated with adverse events when compared with BMS.

Comparison of Ascending Aortic Size in Patients With Severe Bicuspid Aortic Valve Stenosis Treated With Versus Without a Statin Drug

Ascending aortic dilation commonly occurs in patients with bicuspid aortic valve (BAV). Statins have been shown to reduce the expression of matrix metalloproteinases and slow the progression of abdominal aortic aneurysms. The role of statins in slowing ascending aortic dilation in patients with BAV is unknown. We sought to compare the ascending aortic dimensions in patients with BAV stenosis treated with versus without a statin. From our catheterization laboratory database, all patients undergoing preoperative coronary angiography before aortic valve with or without ascending aorta replacement for bicuspid aortic stenosis (AS) from 2004 to 2007 were identified. The ascending aortic size was measured on their preoperative transesophageal echocardiogram. Data on statin use were obtained from chart review, and the ascending aortic size was compared between patients taking and not taking a statin. The study sample included 147 patients, of whom 76 were treated with statins (mean age 62 ± 9 years, 72% men) and 71 were not (mean age 59 ± 12 years, 68% men). The total and low-density lipoprotein cholesterol and triglyceride levels were significantly lower in the statin group. The ascending aorta size was significantly lower in the statin subgroup of the pure severe AS group (3.6 ± 0.7 cm vs 3.9 ± 0.6 cm, p < 0.01) but not in the mixed severe AS and severe aortic regurgitation group. In the pure severe AS group, significantly fewer patients taking a statin had an ascending aorta ≥ 4 cm (29% vs 52%, p < 0.02). On multivariate analysis, statin use was the only independent predictor of aortic size and was associated with a 0.33-cm reduction in aortic size (95% confidence interval 0.06 to 0.59, p < 0.01). In conclusion, patients with statin-treated BAV stenosis have a smaller ascending aortic size than patients with BAV untreated with statins.

Microvolt T-Wave Alternans, Peak Oxygen Consumption, and Outcome in Patients with Severely Impaired Left Ventricular Systolic Function

BACKGROUND Abnormal microvolt T-wave alternans (MTWA) and low peak oxygen consumption (VO2) both predict poor outcome in heart failure. However, their independent predictive properties have not been assessed in large-scale cohorts. METHODS This was an observational prospective cohort study of 303 consecutive patients referred for metabolic stress testing. All had an ejection fraction < or = 40% and were considered candidates for transplantation. The exercise laboratory did not collect MTWA data from patients with implanted pacemakers or defibrillators. The primary end point was a composite of all-cause death or United Network for Organ Sharing status 1 transplantation. RESULTS During a 2.8-year period, there were 34 deaths and 17 transplantations. Patients with abnormal MTWA had a higher event rate of 23% (31 of 136) vs 12% (20 of 167), with an unadjusted hazard ratio (HR) of 1.90 (95% confidence interval [CI], 1.90-3.33; p = 0.03). The association remained significant after adjustment for 3 clinical variables (HR, 1.89; 95% CI, 1.05-3.39; p = 0.03). After adding peak VO2 to the model, the association was no longer significant (adjusted HR, 1.18; 95% CI, 0.64-2.17, p = 0.60). After accounting for peak VO2 and 28 other confounders in a matched propensity analysis, MTWA was not predictive (propensity-matched HR, 0.79; 95% CI, 0.37-1.66; p = 0.53). CONCLUSIONS These results confirm the association of abnormal MTWA with poor outcome amongst patients with impaired left ventricular systolic function. However, this association is markedly attenuated after accounting for peak VO2.