Jeevanantham Rajeswaran

Survival after valve replacement for aortic stenosis: Implications for decision making

OBJECTIVE Recommendations for aortic valve replacement in severe aortic stenosis are based primarily on the presence of symptoms. However, the onset of symptoms is often insidious, potentially leading to delayed intervention and suboptimal results. Identifying factors that reduce the survival of patients undergoing aortic valve replacement could lead to revised treatment guidelines and improved outcomes. METHODS We conducted a single-center observational clinical study of 3049 patients with aortic stenosis who underwent native aortic valve replacement with a single type of bioprosthesis. The primary end point was all-cause mortality from the date of operation. Multivariable analysis of risk factors for death was performed in the multiphase hazard function domain. RESULTS The presence of severe left ventricular hypertrophy at operation, which preceded symptoms in 17% of patients, was associated with decreased survival. This effect was magnified by the severity of aortic stenosis (P = .02) and use of small prostheses (P = .01). The presence of left ventricular dysfunction reduced survival (P = .0003). Although older age was a risk factor for death (P < .0001), elderly patients had survival comparable to their age, race, and sex-matched cohorts, whereas younger patients had worse than expected survival that was further diminished with insertion of a small prosthesis (P = .01). CONCLUSION To optimize survival, earlier aortic valve replacement should be considered even in asymptomatic patients before severe left ventricular hypertrophy or dysfunction develops. In younger patients, the largest possible prosthesis should be implanted to minimize residual gradient; in elderly patients, complex operations just to insert larger prostheses should be avoided.

Surgical management of secondary tricuspid valve regurgitation: Annulus, commissure, or leaflet procedure?

OBJECTIVES Techniques employed today concomitantly with left-sided heart valve surgery address secondary tricuspid valve regurgitation at 3 anatomic levels-annulus, commissure, and leaflet-although success of these alone or in combination in eliminating tricuspid regurgitation is uncertain. Our objective was to assess the comparative effectiveness of these techniques in reducing or eliminating secondary tricuspid regurgitation. METHODS From 1990 to 2008, 2277 patients underwent tricuspid valve procedures for secondary tricuspid regurgitation concomitantly with mitral (n = 1527, 67%), aortic (n = 180, 7.9%), or combined (n = 570, 25%) valve surgery. These included annulus (flexible prosthesis [n = 1052, 46%], rigid prosthesis [standard = 387, 3-dimensional = 197; 26%], Peri-Guard annuloplasty [Synovis Surgical Innovations, St Paul, Minn; n = 185, 8.1%], and De Vega suture [n = 129, 5.7%]), commissure (Kay [n = 248, 11%]), and leaflet (edge-to-edge suture [n = 79, 3.5%] +/- annulus or commissural) procedures. A total of 4745 postoperative transthoracic echocardiograms in 1965 patients were analyzed. RESULTS By 3 months after surgery, only 32% of patients overall had no tricuspid regurgitation. However, by 5 years, this had decreased to 22%, and 3+/4+ tricuspid regurgitation had increased from 11% at 3 months to 17%. Patients with rigid ring annuloplasty alone, either standard or 3-dimensional, had the least increase of 3+/4+ tricuspid regurgitation (to 12% at 5 years) compared with either a commissural or leaflet procedure. CONCLUSION Rigid prosthetic ring annuloplasty, standard or 3-dimensional, provides early and sustained reduction of tricuspid regurgitation secondary to left-sided valve disease without need for an additional leaflet procedure. However, results are imperfect, possibly because other anatomic levels (subvalvular, papillary muscle, and right ventricular) contributing to its pathophysiology are unaddressed.

Minimally invasive versus conventional mitral valve surgery: A propensity-matched comparison

OBJECTIVE Less invasive approaches to mitral valve surgery are increasingly used for improved cosmesis; however, few studies have investigated their effect on outcome. We sought to compare these minimally invasive approaches fairly with conventional full sternotomy by using propensity-matching methods. METHODS From January 1995 to January 2004, 2124 patients underwent isolated mitral valve surgery through a minimally invasive approach, and 1047 underwent isolated mitral valve surgery through a conventional sternotomy. Because there were important differences in patient characteristics, a propensity score based on 42 factors was used to obtain 590 well-matched patient pairs (56% of cases). RESULTS In-hospital mortality was similar for propensity-matched patients: 0.17% (1/590) for those undergoing minimally invasive surgery and 0.85% (5/590) for those undergoing conventional surgery (P = .2). Occurrences of stroke (P = .8), renal failure (P > .9), myocardial infarction (P = .7), and infection (P = .8) were also similar. However, 24-hour mediastinal drainage was less after minimally invasive surgery (median, 250 vs 350 mL; P < .0001), and fewer patients received transfusions (30% vs 37%, P = .01). More patients undergoing minimally invasive surgery were extubated in the operating room (18% vs 5.7%, P < .0001), and postoperative forced expiratory volume in 1 second was higher. Early after operation, pain scores were lower (P < .0001) after minimally invasive surgery. CONCLUSION Within that portion of the spectrum of mitral valve surgery in which propensity matching was possible, minimally invasive mitral valve surgery had cosmetic, blood product use, respiratory, and pain advantages over conventional surgery, and no apparent detriments. Mortality and morbidity for robotic and percutaneous procedures should be compared with these minimally invasive outcomes.

Hemodynamic stability during 17 years of the carpentier-edwards aortic pericardial bioprosthesis☆

BACKGROUND Long-term stability of the hemodynamic performance of commercially available Carpentier-Edwards stented bovine pericardial aortic bioprostheses (Perimount RSR) is unknown. To anticipate the fate of this bioprosthesis, we examined its hemodynamic performance up to 17 years using echocardiographic studies in a Premarket Approval cohort. METHODS Of 267 patients at four institutions in the Premarket Approval cohort, 85 had a total of 168 echocardiographic studies during a 17-year period of yearly follow-up examinations. These were reviewed and quantified in a core echocardiographic facility. Longitudinal data analysis was used to account for repeated, censored data. RESULTS Mean transvalvular gradient was inversely related to prosthesis size (p = 0.01), and possibly (p = 0.06) increased somewhat during the first 10 years of follow-up, then stabilized. Effective orifice area was larger in larger valve sizes (p = 0.01), declined somewhat during the first 10 years, and then began to increase again. Ejection fraction declined minimally (p = 0.2). In contrast to the rather stable hemodynamics, aortic regurgitation steadily increased from none to 1 to 2+ (p = 0.005), but rarely (< 10% at 17 years) progressed to 3+ or 4+. CONCLUSIONS The Carpentier-Edwards aortic pericardial bioprosthesis can be anticipated to have an acceptable long-term transvalvular gradient and effective orifice size that will change trivially up to 17 years after implantation. Mild aortic regurgitation will develop progressively. This anticipated hemodynamic resilience supports continued clinical use of the Perimount Carpentier-Edwards bovine pericardial stented bioprosthesis.

Propensity-Matched Comparisons of Clinical Outcomes After Transapical or Transfemoral Transcatheter Aortic Valve Replacement

Background —Higher risk of adverse outcomes after transapical (TA) vs. transfemoral (TF) transcatheter aortic valve replacement (TAVR) could be due to TA-TAVR being an open surgical procedure or to clinical differences between TA- and TF-TAVR patients. We compared outcomes after neutralizing patient differences using propensity-score matching. Methods and Results —From 4/2007-2/2012, 1100 PARTNER-I patients underwent TA-TAVR and 1521 TF-TAVR using Edwards SAPIEN balloon-expandable bioprostheses. Propensity matching based on 111 pre-procedural variables, exclusive of femoral access morphology, identified 501 well-matched patient pairs (46% of possible matches), 95% of whom had peripheral arterial disease. Matched TA-TAVR patients experienced more adverse procedural events, longer length of stay (5 vs. 8 days, p<0.0001), and slower recovery (New York Heart Association class I 31% vs. 38% at 30 days, equalizing by 6 months at 51% vs. 47%); stroke risk was similar (3.4% vs. 3.3% at 30 days and 6.0% vs. 6.7% at 3 years); mortality was elevated for the first 6 post-procedure months (19% vs. 12%, p=0.01), but aortic regurgitation was less (34% vs. 52% mild and 8.9% vs. 12% moderate-severe at discharge, p=0.001; 36% vs. 50% mild and 10% vs. 15% moderate-severe at 6 months, p<0.0001). Conclusions —Likelihood of adverse periprocedural events and prolonged recovery is greater after TA-TAVR than TF-TAVR in vasculopathic patients after accounting for differences in cardiovascular risk factors, although stroke risk is equivalent and aortic regurgitation less. As smaller delivery systems permit TF-TAVR in many of these patients, we recommend a TF-first access strategy for TAVR when anatomically feasible. Clinical Trial Registration —www.clinicaltrials.gov. Identifier: [NCT00530894][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00530894&atom=%2Fcirculationaha%2Fearly%2F2015%2F03%2F31%2FCIRCULATIONAHA.114.012525.atomBackground— The higher risk of adverse outcomes after transapical (TA) versus transfemoral (TF) transcatheter aortic valve replacement (TAVR) could be attributable to TA-TAVR being an open surgical procedure or to clinical differences between TA- and TF-TAVR patients. We compared outcomes after neutralizing patient differences using propensity score matching. Methods and Results— From April 2007 to February 2012, 1100 Placement of Aortic Transcatheter Valves (PARTNER)-I patients underwent TA-TAVR and 1521 underwent TF-TAVR with Edwards SAPIEN balloon-expandable bioprostheses. Propensity matching based on 111 preprocedural variables, exclusive of femoral access morphology, identified 501 well-matched patient pairs (46% of possible matches), 95% of whom had peripheral arterial disease. Matched TA-TAVR patients experienced more adverse procedural events, longer length of stay (5 versus 8 days; P<0.0001), and slower recovery (New York Heart Association class I, 31% versus 38% at 30 days, equalizing by 6 months at 51% versus 47%); stroke risk was similar (3.4% versus 3.3% at 30 days and 6.0% versus 6.7% at 3 years); mortality was elevated for the first 6 postprocedural months (19% versus 12%; P=0.01); but aortic regurgitation was less (34% versus 52% mild and 8.9% versus 12% moderate to severe at discharge, P=0.001; 36% versus 50% mild and 10% versus 15% moderate to severe at 6 months, P<0.0001). Conclusions— The likelihood of adverse periprocedural events and prolonged recovery is greater after TA-TAVR than TF-TAVR in vasculopathic patients after accounting for differences in cardiovascular risk factors, although stroke risk is equivalent and aortic regurgitation is less. As smaller delivery systems permit TF-TAVR in many of these patients, we recommend a TF-first access strategy for TAVR when anatomically feasible. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

Bicuspid aortic valve surgery with proactive ascending aorta repair.

OBJECTIVES Bicuspid aortic valves are associated with aortic catastrophes, particularly dissection. We examined whether proactive repair of associated dilatation would reduce risk of subsequent aortic dissection or reoperation and whether more aggressive resection is needed in patients undergoing bicuspid aortic valve surgery alone. METHODS From January 1993 to June 2003, 1989 patients (of our total experience of 4316) underwent bicuspid aortic valve surgery. Long-term outcomes of 1810 were analyzed according to aortic size and whether bicuspid aortic valve surgery was performed alone or with aortic repair. RESULTS In-hospital 30-day survival was similar (98.8% valve alone vs 98.9% with aortic repair), with no penalty incurred for concomitant aortic repair. Bicuspid aortic valve-alone patients had worse late survival (75% vs 85% at 10 years, P = .0001), but in the matched cohort survival was nearly identical (85% vs 86%; P = .7). With this strategy, freedom from late aortic events was high in both groups (99% valve alone vs 97% with aortic repair at 10 years; P[log-rank] = .06) and similar in the matched cohort (95% vs 97%; P = .2). Approximately 95% of patients undergoing valve-alone surgery had aortic diameters smaller than 4.6 cm or cross-sectional area/height ratios less than 9.4 cm(2)/m; 80% undergoing valve surgery plus aortic repair had diameters larger than 4.1 cm or ratios greater than 7.3 cm(2)/m. Only 0.2% of events occurred at an aortic diameter size of less than 4.5 cm. CONCLUSIONS Aortic size larger than 4.5 cm or aortic cross-sectional area/height ratio greater than 8 to 10 should be considered triggers for concurrent aortic repair, because there is no added risk, and late survival is better; however, more aggressive resection is unwarranted.

Coronary Artery Disease and Outcomes of Aortic Valve Replacement for Severe Aortic Stenosis

OBJECTIVES The study sought to contrast risk profiles and compare outcomes of patients with severe aortic stenosis (AS) and coronary artery disease (CAD) who underwent aortic valve replacement (AVR) and coronary artery bypass grafting (AS+CABG) with those of patients with isolated AS who underwent AVR alone. BACKGROUND In patients with severe AS, CAD is often an incidental finding with underappreciated survival implications. METHODS From October 1991 to July 2010, 2,286 patients underwent AVR+CABG and 1,637 AVR alone. A propensity score was developed and used for matched comparisons of outcomes (1,082 patient pairs). Analyses of long-term mortality were performed for each group, then combined to identify common and unique risk factors. RESULTS Patients with AS+CAD versus isolated AS were older, more symptomatic, and more likely to be hypertensive, and had lower ejection fraction and greater arteriosclerotic burden but less severe AS. Hospital morbidity and long-term survival were poorer (43% vs. 59% at 10 years). Both groups shared many mortality risk factors; however, early risk among AS+CAD patients reflected effects of CAD; late risk reflected diastolic left ventricular dysfunction expressed as ventricular hypertrophy and left atrial enlargement. Patients with isolated AS and few comorbidities had the best outcome, those with CAD without myocardial damage had intermediate outcome equivalent to propensity-matched isolated AS patients, and those with CAD, myocardial damage, and advanced comorbidities had the worst outcome. CONCLUSIONS Cardiovascular risk factors and comorbidities must be considered in managing patients with severe AS. Patients with severe AS and CAD risk factors should undergo early diagnostics and AVR+CABG before ischemic myocardial damage occurs.

Pericardial delayed hyperenhancement with CMR imaging in patients with constrictive pericarditis undergoing surgical pericardiectomy: a case series with histopathological correlation.

OBJECTIVES The purpose of this study was to examine the prevalence and histopathologic correlates of pericardial delayed hyperenhancement (DHE) seen with cardiac magnetic resonance imaging (CMR) among patients with constrictive pericarditis (CP) undergoing pericardiectomy. BACKGROUND Constrictive pericarditis patients studied by CMR will occasionally demonstrate pericardial DHE following gadolinium contrast administration. METHODS We identified 25 CP patients who underwent pericardiectomy following CMR-gadolinium study. We also assessed 10 control subjects with no evidence of pericardial disease referred for cardiac viability imaging. A novel 14-segment pericardial model was used to determine pericardial DHE score and thickness score. Histopathology of pericardial specimens was reviewed and evaluated semiquantitatively on a 4-point scale for the extent of calcification, fibrosis, inflammation, and neovascularization. RESULTS DHE was present in 12 (48%) CP patients (DHE+ group), and absent in 13 CP patients (DHE- group) and all control patients. The DHE+ group had greater fibroblastic proliferation and neovascularization, as well as more prominent chronic inflammation and granulation tissue. Fibroblastic proliferation and chronic inflammation correlated with DHE presence quantitated by DHE score (Spearman r = 0.578, p < 0.002, and r = 0.590, p < 0.002, respectively), but not with pericardial thickness. Segmental analysis demonstrated no significant difference in the percentage of patients with different pericardial segmental thickness; however, overall, in each segment, the DHE+ group tended to have greater pericardial thickness. CONCLUSIONS The presence of pericardial DHE on CMR is common in patients with CP, and its presence is associated with histological features of organizing pericarditis, which may be a target for future focused pharmacological interventions. Patients with CP without pericardial DHE had more pericardial fibrosis and calcification, as well as lesser degrees of pericardial thickening.

Propensity-Matched Comparisons of Clinical Outcomes After Transapical or Transfemoral Transcatheter Aortic Valve Replacement A Placement of Aortic Transcatheter Valves (PARTNER)-I Trial Substudy

Background —Higher risk of adverse outcomes after transapical (TA) vs. transfemoral (TF) transcatheter aortic valve replacement (TAVR) could be due to TA-TAVR being an open surgical procedure or to clinical differences between TA- and TF-TAVR patients. We compared outcomes after neutralizing patient differences using propensity-score matching. Methods and Results —From 4/2007-2/2012, 1100 PARTNER-I patients underwent TA-TAVR and 1521 TF-TAVR using Edwards SAPIEN balloon-expandable bioprostheses. Propensity matching based on 111 pre-procedural variables, exclusive of femoral access morphology, identified 501 well-matched patient pairs (46% of possible matches), 95% of whom had peripheral arterial disease. Matched TA-TAVR patients experienced more adverse procedural events, longer length of stay (5 vs. 8 days, p<0.0001), and slower recovery (New York Heart Association class I 31% vs. 38% at 30 days, equalizing by 6 months at 51% vs. 47%); stroke risk was similar (3.4% vs. 3.3% at 30 days and 6.0% vs. 6.7% at 3 years); mortality was elevated for the first 6 post-procedure months (19% vs. 12%, p=0.01), but aortic regurgitation was less (34% vs. 52% mild and 8.9% vs. 12% moderate-severe at discharge, p=0.001; 36% vs. 50% mild and 10% vs. 15% moderate-severe at 6 months, p<0.0001). Conclusions —Likelihood of adverse periprocedural events and prolonged recovery is greater after TA-TAVR than TF-TAVR in vasculopathic patients after accounting for differences in cardiovascular risk factors, although stroke risk is equivalent and aortic regurgitation less. As smaller delivery systems permit TF-TAVR in many of these patients, we recommend a TF-first access strategy for TAVR when anatomically feasible. Clinical Trial Registration —www.clinicaltrials.gov. Identifier: [NCT00530894][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00530894&atom=%2Fcirculationaha%2Fearly%2F2015%2F03%2F31%2FCIRCULATIONAHA.114.012525.atomBackground— The higher risk of adverse outcomes after transapical (TA) versus transfemoral (TF) transcatheter aortic valve replacement (TAVR) could be attributable to TA-TAVR being an open surgical procedure or to clinical differences between TA- and TF-TAVR patients. We compared outcomes after neutralizing patient differences using propensity score matching. Methods and Results— From April 2007 to February 2012, 1100 Placement of Aortic Transcatheter Valves (PARTNER)-I patients underwent TA-TAVR and 1521 underwent TF-TAVR with Edwards SAPIEN balloon-expandable bioprostheses. Propensity matching based on 111 preprocedural variables, exclusive of femoral access morphology, identified 501 well-matched patient pairs (46% of possible matches), 95% of whom had peripheral arterial disease. Matched TA-TAVR patients experienced more adverse procedural events, longer length of stay (5 versus 8 days; P<0.0001), and slower recovery (New York Heart Association class I, 31% versus 38% at 30 days, equalizing by 6 months at 51% versus 47%); stroke risk was similar (3.4% versus 3.3% at 30 days and 6.0% versus 6.7% at 3 years); mortality was elevated for the first 6 postprocedural months (19% versus 12%; P=0.01); but aortic regurgitation was less (34% versus 52% mild and 8.9% versus 12% moderate to severe at discharge, P=0.001; 36% versus 50% mild and 10% versus 15% moderate to severe at 6 months, P<0.0001). Conclusions— The likelihood of adverse periprocedural events and prolonged recovery is greater after TA-TAVR than TF-TAVR in vasculopathic patients after accounting for differences in cardiovascular risk factors, although stroke risk is equivalent and aortic regurgitation is less. As smaller delivery systems permit TF-TAVR in many of these patients, we recommend a TF-first access strategy for TAVR when anatomically feasible. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

Comprehensive analysis of mortality among patients undergoing TAVR: results of the PARTNER trial.

BACKGROUND Patients with severe aortic stenosis (AS) who were deemed too high risk or inoperable for conventional aortic valve replacement (AVR) in the PARTNER (Placement of Aortic Transcatheter Valves) trial were randomized to transcatheter aortic valve replacement (TAVR) versus AVR (PARTNER-A arm) or standard therapy (PARTNER-B arm). OBJECTIVES This study compared when and how deaths occurred after TAVR versus surgical AVR or standard therapy. METHODS The PARTNER-A arm included 244 transfemoral (TF) and 104 transapical (TA) TAVR patients, and 351 AVR patients; the PARTNER-B arm included 179 TF-TAVR patients and 179 standard therapy patients. Deaths were categorized as cardiovascular, noncardiovascular, or uncategorizable, and were characterized by multiphase hazard modelling. RESULTS In the PARTNER-A arm, the risk of death peaked after randomization in the TA-TAVR and AVR groups, falling to low levels commensurate with the U.S. population within 3 months. Early risk was less in TF-TAVR patients, resulting in initial superior survival; between 12 and 18 months, risk increased, such that within 2 years, TF-TAVR and AVR patients had similar survival rates. Cardiovascular, noncardiovascular, and uncategorizable deaths for TF-TAVR were 37%, 43%, and 20%, respectively, versus 22%, 41%, and 37%, respectively, for TA-TAVR and 33%, 43%, and 24%, respectively, for AVR. In the PARTNER-B arm, risk with standard therapy was 60% per year; TF-TAVR reduced risk to 20% per year, resulting in 0.5 years of life added within 2.5 years. CONCLUSIONS In inoperable AS patients, TAVR substantially reduced the risk of cardiovascular death. In high-risk patients, TA-TAVR and AVR were associated with elevated peri-procedural risk more than with TF-TAVR, although cardiovascular death was higher after TF-TAVR. Therefore, TF-TAVR should be considered the standard of care for severely symptomatic inoperable patients or those at high risk of noncardiovascular mortality after conventional surgery. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).