**5. Importance and impact of pulmonary hypertension in cardiac surgery**

Preoperative PH is associated with increased morbidity and mortality in cardiac surgery (Tuman et al., 1992; Tremblay et al., 1993; Reich et al., 1999; Bernstein & Parsonnet, 2000; Malouf et al., 2002). Therefore, awareness of PH is very important and its presence in any form should be routinely reported to the surgeon and be evaluated in risk stratification models. Yet, this is not always the case, since only 4/19 risk stratification models in cardiac surgery include preoperative PH as a risk factor (Nilsson et al., 2006). Interestingly, PH is included in the EuroSCORE model which had the greatest discriminatory power over all other models. In a Swedish study including 4351 CABG patients, the receiver operating characteristics (ROC) of the EuroSCORE model was found to be 0.86 and 0.75 for the 30-day and one year mortality rates, respectively.

Analysis performed using the Montreal Heart Institute anesthesia database in 1999 on a total of 1439 patients revealed a mean preoperative SPAP of 31±10 mmHg. PH was defined as SPAP > 30 mmHg and was observed in 605 patients (42%). The type of procedures performed in this subpopulation were mainly MVR (*n*=80, 40±14 mmHg), followed by combined CABG and valve procedures (*n*=126, 36±13 mmHg), multiple valve procedures (*n*=60, 36±16 mmHg) and heart transplantations (*n*=6, 36±14 mmHg). Severe PH defined as MAP/MPAP ratio < 2 was observed in 16 patients, who all experienced difficult separation from CPB, half of them required postoperative vasoactive support for more than 24 hours while 3 of them died (18.7%).

Thus, PH present before, during or after the operation has an impact on survival mostly through its deleterious effect on right-sided heart function. The most dreaded consequence of PH is the increase in RV afterload and RV dysfunction which will be addressed herein.

### **5.1 Right ventricular dysfunction**

Regardless of the underlying cause, uncontrolled PH leads to RV dysfunction. There is growing evidence showing that morbidity and mortality associated with PH depends on RV adaptation to the disease rather than on the absolute values of PAP (D'Alonzo et al., 1991; Yeo et al., 1998; Ramakrishna et al., 2005; Voelkel et al., 2006; Haddad et al., 2009). Furthermore, studies addressing hemodynamic variables and survival in idiopathic pulmonary arterial hypertension show that high mean Pra and low CO are consistently associated with poorer survival while PAP values are only moderately related to outcome (D'Alonzo et al., 1991; Chin et al., 2005).

Many studies, in a variety of clinical settings, have demonstrated the importance of RV function in cardiac surgery (Table **3**) (Haddad et al., 2009). Typical pathologies and treatments in these studies included high risk coronary or valvular heart disease, congenital heart disease, heart transplantation, patients requiring mechanical assist devices, and unstable patients postoperatively. However, most of the evidence supporting the importance of RV function pertains to retrospective and small prospective studies. Moreover, parameters of RV function have not yet been included in large scale models of risk stratification and thus, their incremental value to the Parsonnet Score and the EuroSCORE has not been well established (Bernstein & Parsonnet, 2000; Nashef et al., 2002; Shroyer et al., 2003; Ambler et al., 2005). A panel in 2006 from the National Institute of Health (NIH) has emphasized the importance of conducting research to better understand RV failure (Voelkel et al., 2006).

#### **5.1.1 Before the procedure**

In patients with severe aortic stenosis, Boldt *et al.* (Boldt et al., 1992) demonstrated that preoperative RV dysfunction was associated with increased requirements for postoperative inotropic support.


CAD: coronary artery disease; LVEF: left ventricular ejection fraction; LVAD: left ventricular assist device; RV: right ventricular; RVAD: right ventricular assist device; RVESV: right ventricular endsystolic volume; RVEDV: right ventricular end-diastolic volume; RVEF: right ventricular ejection fraction; RVFAC: right ventricular fractional area change; RVMPI: right ventricular myocardial performance index; RVOTO: right ventricular outflow tract obstruction. (Haddad et al., 2009)

Table 3. Prognostic Value of Right Ventricular Function in Cardiac Surgery (selected studies)

294 Perioperative Considerations in Cardiac Surgery

form should be routinely reported to the surgeon and be evaluated in risk stratification models. Yet, this is not always the case, since only 4/19 risk stratification models in cardiac surgery include preoperative PH as a risk factor (Nilsson et al., 2006). Interestingly, PH is included in the EuroSCORE model which had the greatest discriminatory power over all other models. In a Swedish study including 4351 CABG patients, the receiver operating characteristics (ROC) of the EuroSCORE model was found to be 0.86 and 0.75 for the 30-day

Analysis performed using the Montreal Heart Institute anesthesia database in 1999 on a total of 1439 patients revealed a mean preoperative SPAP of 31±10 mmHg. PH was defined as SPAP > 30 mmHg and was observed in 605 patients (42%). The type of procedures performed in this subpopulation were mainly MVR (*n*=80, 40±14 mmHg), followed by combined CABG and valve procedures (*n*=126, 36±13 mmHg), multiple valve procedures (*n*=60, 36±16 mmHg) and heart transplantations (*n*=6, 36±14 mmHg). Severe PH defined as MAP/MPAP ratio < 2 was observed in 16 patients, who all experienced difficult separation from CPB, half of them required postoperative vasoactive support for more than 24 hours

Thus, PH present before, during or after the operation has an impact on survival mostly through its deleterious effect on right-sided heart function. The most dreaded consequence of PH is the increase in RV afterload and RV dysfunction which will be addressed herein.

Regardless of the underlying cause, uncontrolled PH leads to RV dysfunction. There is growing evidence showing that morbidity and mortality associated with PH depends on RV adaptation to the disease rather than on the absolute values of PAP (D'Alonzo et al., 1991; Yeo et al., 1998; Ramakrishna et al., 2005; Voelkel et al., 2006; Haddad et al., 2009). Furthermore, studies addressing hemodynamic variables and survival in idiopathic pulmonary arterial hypertension show that high mean Pra and low CO are consistently associated with poorer survival while PAP values are only moderately related to outcome

Many studies, in a variety of clinical settings, have demonstrated the importance of RV function in cardiac surgery (Table **3**) (Haddad et al., 2009). Typical pathologies and treatments in these studies included high risk coronary or valvular heart disease, congenital heart disease, heart transplantation, patients requiring mechanical assist devices, and unstable patients postoperatively. However, most of the evidence supporting the importance of RV function pertains to retrospective and small prospective studies. Moreover, parameters of RV function have not yet been included in large scale models of risk stratification and thus, their incremental value to the Parsonnet Score and the EuroSCORE has not been well established (Bernstein & Parsonnet, 2000; Nashef et al., 2002; Shroyer et al., 2003; Ambler et al., 2005). A panel in 2006 from the National Institute of Health (NIH) has emphasized the importance of conducting research to better understand

In patients with severe aortic stenosis, Boldt *et al.* (Boldt et al., 1992) demonstrated that preoperative RV dysfunction was associated with increased requirements for postoperative

and one year mortality rates, respectively.

while 3 of them died (18.7%).

**5.1 Right ventricular dysfunction** 

(D'Alonzo et al., 1991; Chin et al., 2005).

RV failure (Voelkel et al., 2006).

**5.1.1 Before the procedure** 

inotropic support.

In a retrospective study involving patients undergoing mitral and mitral-aortic valvular surgery, Pinzani *et al*. (Pinzani et al., 1993) showed that preoperative RV failure was associated with increased perioperative mortality. Furthermore, in that study, postoperative RV failure was the most important independent predictor of late survival.

In a small prospective study of 14 patients with severe non-ischemic mitral regurgitation presenting high risk descriptors (LV ejection fraction (LVEF) 45% or RVEF 20%), Wencker *et al*. (Wencker et al., 2000) found that preoperative RVEF 20% predicted late postoperative death.

In a retrospective study of 41 patients undergoing non-emergent coronary artery bypass surgery, Maslow *et al.* (Maslow et al., 2002) have shown than RV dysfunction (right ventricular fractional area change (RVFAC)< 35%) in presence of severe LV dysfunction (LVEF ≤ 25%) was associated with an increased risk of postoperative morbidity and mortality. Furthermore, patients with RV dysfunction presented a higher prevalence of diabetes mellitus and renal disease, a higher incidence of postoperative support (inotropic or mechanical), longer ICU and hospital stays, as well as a decrease in short and long term survival.

#### **Experience at the Montreal Heart Institute**

Haddad *et al.* (Haddad et al., 2007) further assessed the value of RV function relative to other validated risk factors in open valvular heart surgery on 50 patients undergoing valvular surgery. Patients with RV myocardial performance index (RVMPI) < 50% (*n*=20) presented a significantly higher occurrence of circulatory failure (16/20 (80%) *vs* 6/30 (20%), p<0.0001) as well as a higher postoperative heart failure mortality (14/20 (74%) *vs* 3/30 (10%), p<0.0001). In addition, multivariate analysis revealed RVMPI as the only independent predictor of heart failure and mortality among all other demographic, hemodynamic and echocardiographic variables (p<0.0001).

#### **5.1.2 After the procedure**

Right ventricular failure after CPB is associated with a mortality rate ranging from 44% to 86% (Davila-Roman et al., 1995). The incidence of acute refractory RV failure ranges from 0.04 to 0.1% after cardiac surgery. Acute refractory RV failure has also been reported in 2-3% patients after heart trasplantationand in 20-30% patients receiving support from a LV assist device with a reported initial salvage rate as low as 25-30% (Kaul & Fields, 2000).
