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Ann Thorac Surg 2006;82:879-888
© 2006 The Society of Thoracic Surgeons
a Division of Cardiac Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland
b Division of Radiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
Accepted for publication April 3, 2006.
* Address correspondence to Dr Conte, Division of Cardiac Surgery, Heart and Lung Transplantation, Johns Hopkins Medical Institutions, Blalock 618, 600 N Wolfe St, Baltimore, MD 21287. (Email: jconte{at}csurg.jhmi.jhu.edu).
Presented at the Forty-second Annual Meeting of The Society of Thoracic Surgeons, Chicago, IL, Jan 30–Feb 1, 2006.
| Mr Patel and Dr Conte disclose that they have a financial relationship with Chase Medical Corp.
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Abstract |
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 Top Abstract IntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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METHODS: We retrospectively reviewed SVR patients between January 2002 and June 2005. Patients were classified as PHTN (mean pulmonary artery pressure 
25 mm Hg) and no PHTN (mPAP < 25 mm Hg) based on preoperative cardiac catheterization. Cardiac function was assessed using magnetic resonance imaging and echocardiography. Follow-up was 100%.
RESULTS: Sixty-nine patients underwent SVR for congestive heart failure. Thirty-six percent (25 of 69) had preoperative PHTN. Preoperatively, PHTN patients had significantly lower ejection fraction (21.1% versus 30.0%; p = 0.005) and larger left ventricular end-systolic volume index (119.0 versus 88.7 mL/m2; p = 0.04) than patients without PHTN. All PHTN patients and 95.5% (42 of 44) of the no PHTN group were New York Heart Association (NYHA) class III/IV preoperatively. There was 1 operative death in the PHTN group. Surgical ventricular restoration significantly improved cardiac function and pulmonary pressures for PHTN patients. Both groups had similar cardiac function postoperatively. Seventy-two percent (18 of 25) of PHTN patients and 69.0% (29 of 42) of patients without PHTN improved to NYHA class I/II at follow-up. Kaplan-Meier survival of PHTN patients was 68.1% at 3 years, which was lower than patients without PHTN (81.4%; p = 0.44), but not statistically significant. Kaplan-Meier 3-year survival for all SVR patients was 76.6%.
CONCLUSIONS: Surgical ventricular restoration is a good treatment option in patients with advanced congestive heart failure and PHTN. Our early results are promising and should prompt further studies to confirm these findings.
Approximately 5 million Americans currently suffer from congestive heart failure (CHF), and this number is increasing annually [1]. Patients with advanced CHF have a poor 2-year survival of approximately 50% with medical therapy [2, 3].
Left ventricular dysfunction decreases left ventricular unloading and can result in increased pulmonary vascular resistance and elevated pulmonary pressures. Pulmonary hypertension (PHTN) is defined as a mean pulmonary artery pressure of 25 mm Hg or more at rest [4] and has been shown to be a predictor of death in patients with ischemic cardiomyopathy [5].
Limitations in medical therapy and a paucity of surgical alternatives have led to poor survival among CHF patients diagnosed with PHTN. Cardiac transplantation is the gold standard for the treatment of CHF. Studies have demonstrated reduced pulmonary artery pressures and pulmonary vascular resistance after cardiac transplantation [6, 7]. However, severely elevated pulmonary artery pressures and pulmonary vascular resistance are a contraindication to cardiac transplantation because of concerns about right ventricular failure postoperatively [8, 9]. Other surgical options are needed to improve survival for CHF patients with PHTN.
Surgical ventricular restoration (SVR) attempts to reverse the morphologic changes of postinfarction ventricular remodeling. Its goal is to reduce the size of the left ventricle, restore a more normal elliptical shape to the left ventricle, reduce myocardial wall stress, and improve cardiac function. Recent SVR studies have demonstrated excellent survival and improvements in ejection fraction (EF), left ventricular volumes, and New York Heart Association (NYHA) functional class [10–16]. Furthermore, SVR improves mechanical intraventricular dyssynchrony [17] and normalizes neurohormone abnormalities seen with CHF [18]. Surgical ventricular restoration has also led to significant improvement in cardiac function and survival in patients with clinically advanced CHF and severely depressed EF [15], and in patients with multiterritory myocardial infarction [16], both traditionally considered high risk for SVR.
Commonly accepted indications for SVR include anterior wall myocardial infarction, left ventricular enlargement, and a large area of akinesia or dyskinesia. These patients usually have a depressed EF, clinical signs of CHF, and may have angina, inducible ischemia, or arrhythmias [10–16]. Pulmonary hypertension has been considered a relative contraindication to SVR because of a presumed increase in operative risk among already high-risk surgical candidates. However, few studies have specifically described SVR outcomes in patients with advanced CHF and PHTN. This study was undertaken to analyze early outcomes, survival, and the impact of SVR on pulmonary pressures in CHF patients with PHTN.
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Patients and Methods |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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Patient Variables
Data collection included demographics, NYHA functional status, hemodynamics, postoperative complications and procedures, and quality of life data. Magnetic resonance imaging and echocardiography were used to measure left ventricular ejection fraction, left ventricular end-systolic volume index (LVESVI), left ventricular end-diastolic volume index (LVEDVI), and stroke volume index. Quality of life was assessed by telephone interview using the Short-Form 12 (SF-12) questionnaire.
Operative Technique
Our surgical technique has been previously described [15, 16, 19]. Surgical ventricular restoration was performed after coronary artery bypass graft surgery and mitral valve repair/replacement, if necessary.
Perioperative Management
Our routine preoperative management of SVR patients with and without PHTN includes optimizing these patients to medical therapy, including beta blockers, afterload reducers, and diuretics. Preoperatively, inotropes were used in 24.0% (6 of 25) of PHTN patients and 13.6% (6 of 44) of patients without PHTN. The decision to place an intra-aortic balloon pump is made based on the surgeon's assessment of myocardial function and the ability to wean the patient off of cardiopulmonary bypass. Our indication for intra-aortic balloon pump placement is the same for patients with or without PHTN. Nitric oxide, if used, is administered while weaning from cardiopulmonary bypass if the patient exhibits evidence of right heart dysfunction while on adequate inotropic support. All patients were weaned off of cardiopulmonary bypass on epinephrine alone or in combination with other inotropes and vasoconstrictors with the plan to transition to vasodilators and a standard heart failure medical regimen before removing the Swan-Ganz catheter. Postoperatively, patients are followed in the Heart Failure clinic, and we recommend magnetic resonance imaging and echocardiographic evaluation at 6 months and annually thereafter.
Statistical Analysis
Statistical analyses were performed with SPSS 12.0 software (SPSS, Chicago, Illinois). Fisher's exact test and t test were used for qualitative and quantitative variable analyses, respectively. Cox regression analysis was used to determine if PHTN was a predictor of mortality in patients undergoing SVR. Furthermore, we conducted Cox regression analysis to determine predictors of mortality for the PHTN group. Kaplan-Meier and log-rank analyses were performed to compare survival for patients with and without PHTN.
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Results |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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Ejection Fraction and Left Ventricular Volumes
Preoperative magnetic resonance imaging demonstrated that patients with PHTN had a significantly lower EF (21.1% ± 9.4% versus 30.0% ± 10.9%; p = 0.005) and a larger LVESVI (119.0 ± 68.0 mL/m2 versus 88.7 ± 37.3 mL/m2; p = 0.04) than patients without PHTN. Preoperative LVEDVI (147.4 ± 69.0 mL/m2 versus 122.9 ± 37.9 mL/m2; p = 0.12) and stroke volume index (28.5 ± 8.6 mL/m2 versus 34.1 ± 10.3 mL/m2; p = 0.05) were not statistically different between the two groups.
Surgical ventricular restoration significantly improved EF, LVESVI, and LVEDVI for both groups on magnetic resonance imaging and echocardiography (Table 2). When comparing patients with PHTN and those without PHTN, there were no significant differences in postoperative EF (34.4% ± 8.7% versus 38.8% ± 10.8%; p = 0.22), LVESVI (68.8 ± 24.4 mL/m2 versus 62.6 ± 31.1 mL/m2; p = 0.54), LVEDVI (104.1 ± 29.3 mL/m2 versus 99.2 ± 37.4 mL/m2; p = 0.69), or stroke volume index (35.3 ± 11.3 mL/m2 versus 35.7 ± 11.1 mL/m2; p = 0.92). The percent improvements in EF, LVESVI, and LVEDVI for the PHTN group were 63.0%, 42.2%, and 29.4%, respectively, which were greater than those in patients without PHTN (29.3%, 29.4%, and 19.3%, respectively).
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Length of Stay, Length of Intubation, and Postoperative Complications
Length of stay data and postoperative complications are listed in Table 3
and are similar between the two groups. Mean length of intubation while in the intensive care unit for the PHTN group was 4.6 ± 11.9 days (median, 1 day), which was similar to patients without PHTN (4.8 ± 11.6 days; median, 1 day; p = 0.93). Also, 24.0% of PHTN patients (6 of 25) and 15.9% of patients without PHTN (7 of 44) were treated with inhaled nitric oxide while in the intensive care unit (p = 0.52).
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Total follow-up for our entire series is 1,211 patient-months (range, 0 to 38.8). Actuarial survival (including hospital deaths) for SVR patients with PHTN at 3 years was 68.1% ± 10.1%. This was lower than the 3-year survival for patients without PHTN (81.4% ± 5.9%; Fig 3), but was not statistically significant. Three-year actuarial survival for all patients undergoing SVR was 76.6% ± 5.4%. Freedom from left ventricular assist device, cardiac transplantation, and death was 69.5% ± 9.7% and 72.6% ± 10.0% at 3 years for patients with and without PHTN, respectively (Fig 4).
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Cox Regression Model
Cox regression analysis for predictors of mortality in all SVR patients did not identify PHTN (OR = 2, 95% confidence interval [CI]: 0.42 to 9.96, p = 0.38) as a risk factor for mortality. Renal insufficiency (creatinine > 1.5 mg/dL) was found to be a predictor of mortality (OR = 8, 95% CI: 1.01 to 66.1, p = 0.02) for patients undergoing SVR. Furthermore, Cox regression analysis for predictors of mortality in the PHTN group did not identify any predictors of mortality. More importantly, mPAP (OR = 1, 95% CI: 0.95 to 1.18, p = 0.34) was not a risk factor for mortality in PHTN patients.
Functional Outcomes
Surgical ventricular restoration significantly improved functional outcomes for patients with PHTN. Preoperatively, all patients were in either NYHA class III (40%) or class IV (60%), which improved to 28% (7 of 25) at follow-up (p < 0.0001). Thirty-two percent of PHTN patients (8 of 25) and 40% of PHTN patients (10 of 25) improved to NYHA class I and II, respectively (Fig 5). In patients without PHTN, similar improvements in NYHA status were observed with 69.0% (29 of 42) of patients in preoperative NYHA class III or IV improving to class I or II at follow-up.
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Comment |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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Pulmonary hypertension is presently considered a relative contraindication for SVR, but has not been thoroughly studied. The studies that have included data on PHTN have done so without a great deal of data or focus. In a recent study of 245 consecutive SVR patients, Di Donato and colleagues [12] reported a mean preoperative mPAP of 21 mm Hg. Some patients in this study certainly had PHTN, but the authors did not assess the impact of PHTN on survival and outcomes after SVR. Another study reported that preoperative mPAP at systemic levels were considered inoperable, but did not discuss what level of PHTN was considered operable or how many patients in the series had PHTN [14].
Two studies from Dor and associates [21, 22] provided some information on PHTN, but did not directly study the issue. The first [21] found that patients with a basal mPAP greater than 28 mm Hg demonstrated improvements in EF, LVESVI, and cardiac index. However, survival data for this group were not reported. In another study, the authors reported a late increase in mPAP 1 year after SVR; 9 of 46 patients with a preoperative mPAP less than 40 mm Hg showed a mPAP greater than 40 mm Hg at 1 year [22]. The authors attributed the rise in mPAP at 1 year to the reduced compliance of the left ventricle due to SVR; the impact of PHTN on survival was not assessed.
A report from Di Donato and associates [23] studied outcomes in patients undergoing endoventricular patch plasty for akinetic versus dyskinetic scar. In this study, the authors demonstrated that survivors had a significantly lower mean preoperative mPAP (22 mm Hg) than nonsurvivors (33 mm Hg) and found that a preoperative mPAP greater than 33 mm Hg was an independent predictor of mortality. Although an evaluation of PHTN and its impact on survival was reported, the authors did find that PHTN had a negative impact on survival.
Despite the excellent results reported in the literature, no studies have focused on outcomes and survival among SVR patients with PHTN. Our results demonstrate significant improvements in EF, LVESVI, and LVEDVI in patients with PHTN. Furthermore, patients with PHTN demonstrated significant improvements in pulmonary pressures, cardiac index, pulmonary vascular resistance index, and right ventricular stroke work index after SVR.
We identified 10 patients with moderate to severe PHTN (mPAP 40 mm Hg). Our outcomes in patients with severe PHTN were acceptable, with no operative mortalities. Postoperatively, 7 of these 10 patients improved to NYHA class I or II. The remaining 3 patients who were in postoperative NYHA class IV died with moderate to severe PHTN. Although these data are limited to 10 patients with moderate to severe PHTN, our preliminary results are encouraging and show that even those with moderate to severe PHTN can be operated on successfully.
Mitral regurgitation is common in patients with left ventricular dilatation and likely plays a role in the etiology of PHTN in some patients. Although some patients may demonstrate improved mitral valve function after SVR alone, our current policy is to perform a mitral valve procedure in all patients who demonstrate worse than mild mitral regurgitation on preoperative echocardiography. Mitral valve repair or replacement is especially important in PHTN patients with mitral regurgitation, as repairing or replacing the valve may assist in reducing pulmonary pressures. It is important to note that only 7 of the 25 PHTN patients, 3 of whom had moderate to severe PHTN, underwent a mitral valve procedure for significant mitral regurgitation. The remaining 18 of the 25 PHTN patients had PHTN without significant mitral regurgitation, signifying the role of severe left ventricular dysfunction in the etiology of PHTN in these patients.
One of the major limitations of our study is its retrospective nature and the impact this had on our ability to report and interpret hemodynamic indices. There was not a protocol-driven management of inotropes and hemodynamic indices in this study. Therefore, the combination of medicines, the timing of collecting hemodynamic measurements, the weaning of drugs, and the removal of the Swan-Ganz catheters were determined by the clinical judgment of many intensive care unit providers. In this setting, some patients in both groups had their last hemodynamic measurements influenced by inotropic and vasoactive medications. Since this was the same for both groups in this study, it is unlikely that this impacted either group preferentially. What can be said is that all patients were weaned off cardiopulmonary bypass on epinephrine and were maintained on that alone, or with other inotropic and vasoactive medications for at least 24 hours. Despite this limitation, we believe, and our data show, that improved left ventricular function after SVR reduces the load on the pulmonary vasculature, and ultimately lowers pulmonary resistance and pulmonary pressures in patients with and without PHTN.
Kaplan-Meier survival for CHF patients with PHTN was 68% at 3 years, which is improved compared with CHF patients treated with optimal medical therapy [24, 25]. As our data show, patients with PHTN are arguably a sicker group of patients. Although survival was lower among PHTN patients than among patients without PHTN, this difference was not found to be significant on log-rank analysis. However, a limitation of our study is that it is not powered for survival given the small patient population and the relatively short follow-up. The limited number of patients in our study may mask any true differences in survival between patients with and without PHTN. Survival in patients with PHTN in this series is slightly lower than survival of traditional SVR patients reported by other centers [10–14]. Nevertheless, it is important to recognize that patients in this series comprise a sicker population than those reported by other authors. Mickleborough and associates [14] report an excellent survival of 82% at 5 years for patients undergoing SVR, but only 61% were CHF patients in NYHA class III or IV. They did provide data showing that CHF patients have a significantly worse survival than those without CHF, but like many others, did not investigate the impact of PHTN on outcomes.
The Reconstructive Endovascular Surgery returning Torsion Original Radius Elliptical Shape multicenter study reports a 3-year survival of approximately 80% for patients in NYHA class III and 65% for those in class IV [[13]. The authors also demonstrate that patients with a preoperative EF less than 30% and an LVESVI greater than 80 mL/m2 have a 3-year survival of 75% and 70%, respectively. Similarly, Di Donato and colleagues [12], in a study of 245 patients, demonstrated excellent survival, but only 61% had CHF and 54% were NYHA class III or IV status preoperatively. All PHTN patients and 95% of non-PHTN patients in this study were in preoperative NYHA class III or IV, which is a larger percentage of the cohort when compared with other studies [13, 14].
We have shown that SVR significantly improves cardiac function and hemodynamic parameters in patients with CHF and PHTN. The significance of this study is not whether PHTN patients have equal outcomes after SVR when compared with patients without PHTN. Pulmonary hypertension patients are sicker, and the survival for these patients may in fact be less than the survival for patients without PHTN. The significance is that even for patients with PHTN, SVR can provide outcomes far superior to the expected outcomes of medically treated patients, and it should be considered a treatment option. Our early and midterm clinical results of SVR for CHF patients with PHTN are encouraging, but a larger patient cohort and longer follow-up are necessary to determine if SVR is beneficial in the long term.
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Discussion |
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DR WILLIAMS: Thank you, Dr Jeevanandam, that is an excellent question. We have not necessarily excluded anyone based on their pulmonary artery (PA) pressures. At our institution, we prefer to focus on global cardiac function when determining whether or not a patient is a good candidate for SVR. If a patient does not have a discrete area of viable myocardium, meaning that they really have global hypokinesis, we would tend to exclude such a patient from undergoing this procedure. Since the vast majority of our patients with pulmonary hypertension have exhibited significant improvement, we have not used the degree of pulmonary hypertension as an exclusion criterion at our institution.
DR VIVEK RAO (Toronto, Ontario, Canada): I would like to congratulate you as well. I want to tease out these pulmonary hypertensives a little bit more. You didn't give us any data with respect to central venous pressures in these patients. So were some of these patients with high PA pressures just wet, and do you have a protocol for introducing inotropic support preoperatively in some of these patients? And secondly, I am more worried about the patient who might have low PA pressures and a really poor right ventricle. Maybe you should get together with Dr Jeevanandam and come up with that right ventricular index that he presented to see which patients really are at risk for failing this operation.
DR WILLIAMS: Thank you, Dr Rao. I think those are excellent points as well. With regard to the central venous pressure, these patients did not have significantly elevated right heart pressures before undergoing SVR. Furthermore, only 4 of these patients had significant tricuspid regurgitation preoperatively. So I think we can be fairly confident that we are seeing patients with true pulmonary hypertension, and not patients with poor right ventricular function and volume overload.
With regard to your question about preoperative inotrope use, we don't have a standard protocol at our institution. We evaluate patients on an individual basis and use all means necessary to medically optimize them before surgery. Certainly, if a patient requires inotropic support preoperatively, we do not hesitate to start them on those medications.
With regard to the evaluation of right ventricular function in these patients, we have not been able to specifically address that issue using our current magnetic resonance imaging technology. However, we have begun working with some of our colleagues in radiology to develop technology that can better evaluate the right ventricle. Hopefully, this will allow us to address this question in more detail in the near future.
DR LORENZO A. MENICANTI (Milan, Italy): Congratulations for this outstanding presentation, but I would like to have, if possible, more information about surgery of the mitral valve. There is a consistent group in this study in which the mitral valve was approached in a different way. Did you find any differences in the patients with pulmonary hypertension that did or did not have surgery on the mitral valve?
DR WILLIAMS: Thank you, Dr Menicanti, and I would like to acknowledge your pioneering efforts in this field. Surgical ventricular restoration would not be where it is today without your contributions and leadership. Indeed, there was a subset of patients in the pulmonary hypertension group with moderate to severe mitral regurgitation who required a concomitant mitral valve procedure. On subset analysis of these patients, we did not note any preoperative or postoperative differences in these patients when we compared them with pulmonary hypertension patients without significant mitral regurgitation. However, as you indicated, the number of patients in this subset is small, so it is a little bit difficult to draw definitive conclusions from these data. But based on our analysis of the patients we currently have in this cohort, we did not see differences between those groups.
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Acknowledgments |
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p = 0.0001; 
p = 0.03; 
p < 0.0001.
