Results
Patient demographics and baseline characteristics
Patient demographics and baseline characteristics were shown in Table 1.
The mean follow-up duration was 82 months, ranging from 70 to 175
months. None were lost to follow-up. There were 27 men (44.3%) and 34
women (55.7%). Age ranged between 42 and 77 years, with a mean of 58.6
± 11.0 years. 24.6% had dyspnea with mild exertion or minimal activity,
corresponding to New York Heart Association (NYHA) functional class III
or IV status. 57.4% had a prior hospitalization for acute decompensated
heart failure. 73.8% (n=45) had normal left ventricular ejection
fraction. One in four patients had moderate-to-severe pulmonary
hypertension, as defined by mean pulmonary arterial pressures.
Data regarding right ventricular systolic function was missing in 15
patients (21.7%) due to institutional database purge of aged data. For
the patients with available data, one in five had right ventricular
systolic dysfunction.
8.2% of the operations were performed on an urgent basis due to
refractory heart failure or repeated hospitalizations for heart failure.
6.6% had prior cardiac surgery.
Operative details
Operative details were shown in Table 2. 86.9% (n=53) had mechanical
aortic and mitral valve replacement. All tricuspid valves were
successfully repaired. The aetiology of the aortic and mitral valve
dysfunction was predominantly rheumatic (70.5%) and degenerative
(26.2%). One patient had active aortic and mitral valve endocarditis at
the time of surgery. Concomitant CABG was performed in six cases. The
crossclamp and cardiopulmonary bypass times were 186 ± 30 and 132 ± 24
minutes, respectively.
Postoperative
complications
Postoperative complications were shown in Table 3. 6.6% of patients
required resternotomy for haemostasis. Perioperative cerebrovascular
events were not uncommon. Four patients had an ischaemic stroke, and one
became debilitated as a result; two patients suffered from intracranial
haemorrhage which required neurosurgical intervention. None required
permanent pacemaker implantation. 13.1% required renal replacement
therapy due to acute renal failure, another 13.1% required prolonged
ventilation.
Operative mortality and its association with pre-existing
hepatorenal dysfunction
The prevalence and severity of hepatorenal dysfunction was shown in
Table 4. 27.9% of all patients had at least one biochemical
abnormality, namely hyponatremia (defined as plasma sodium less than
135mEq/L), hyperbilirubinemia (total bilirubin ≥ 2.0mg/dL),
hypoalbuminemia (albumin <3.5g/dL) and elevated serum
creatinine (over 200 ųmol/L or dialysis). One in ten patients had two or
more deranged biochemical parameters.
MELD-Na was used as a surrogate measure of the severity of hepatorenal
dysfunction. Most patients had a MELD-Na score less than 9 (68.9%),
26.2% had a moderately elevated score of 9 to 15, and 4.9% had a
severely elevated score of greater than 15.
There were six operative deaths. One patient died from a perforated
peptic ulcer and refractory sepsis. Five deaths can be attributed to
multiorgan failure. The most common cause of demise was exacerbation of
pre-existing hepatorenal dysfunction by cardiopulmonary bypass, systemic
venous congestion, and post-bypass right ventricular dysfunction,
culminating in frank multiorgan failure. Despite instititution of
intra-aortic counter-pulsation and dialysis to reduce right ventricular
afterload and right-sided filling pressures, mortality remained high.
Patients who died exhibited more profound pre-existing hepatorenal
dysfunction than those who survived, as reflected by a higher MELD-Na,t (61) = 8.91, p < 0.001.
Unadjusted operative mortality increased with increasing MELD-Na score,
χ2(2) = 23.8, p = 0.000007. Kendall’s tau (τb) was
0.551, indicating a moderate association. Patients with a MELD-Na
greater than 9 also suffered from more complications, including
postoperative mechanical circulatory support, prolonged ventilation,
need for dialysis and acute liver failure after TVS (Table 5).
A scatterplot of the MELD-Na and EuroSCORE values of the cohort
segregated into survivors and non-survivors were shown in Figure 1 to
facilitate visual comparison. The diagnostic accuracy of MELD-Na was
compared with EuroSCORE using area under the receiver operating
characteristic (ROC) curves. For MELD-Na score, the AUC was an
impressive 0.992 [95% CI 0.925-1.000], indicating high diagnostic
accuracy. The Youden Index was 0.982 at a cut-off of 13. For EuroSCORE,
the AUC was 0.611 [95% CI 0.477-0.733], indicating low diagnostic
accuracy.
Risk-adjusted association of MELD-Na with operative
mortality and major
morbidities
A hierarchical logistic regression model incorporating MELD-Na was
constructed with the logistic EuroSCORE as the base model. EuroSCORE
alone is weakly associated with operative mortality with an odds ratio
of 1.135 [95% CI 1.016 – 1.268] (p = 0.025). After adjustment for
baseline EuroSCORE, the regression model demonstrated continued
associations between MELD-Na and operative mortality and morbidities
(Table 6). Of note, each point of MELD-Na score increase was associated
with 1.405 times increase in the odds of operative mortality (p =
0.015).
The regression analysis was repeated by incorporating individual
components of the MELD-Na score, including bilirubin, sodium, and
albumin. All three biochemical parameters were significantly associated
with operative mortality (Table 7). Creatinine was excluded because it
already is a component of the logistic EuroSCORE.
Long-term survival and cardiac events
Using the Kaplan-Meier method, the 5-year overall and event-free
survival was 78.6% and 72.1% respectively (figure 2 panel A and B).
12.7% of patients had at least one subsequent hospitalization for
congestive heart failure. There were two incidences of late prosthetic
valve endocarditis and one patient died from septic shock. One patient
suffered from structural valve degeneration of the bioprosthetic aortic
valve requiring reoperation.
A total of 20 major bleeding events occurred over 424 person-years of
follow-up. The unadjusted rate of bleeding with warfarin was 4.72% per
person-year. The most common source of bleeding was from the
gastrointestinal tract accounting for half of all bleeding events.