Left-sided valvular heart disease and survival in out-of-hospital cardiac arrest: a nationwide registry-based study

We included 55,615 patients of whom 1948 had AS, 384 had AR, 17 had MS, and 704 had MR. Patients with MS will not be described henceforth due to the low number of cases.

Characteristics prior to cardiac arrest

Figure 1A shows Cox adjusted survival curves (survival time depicts time from valvular diagnosis to cardiac arrest). The adjusted median time from valvular diagnosis to cardiac arrest was 3.7 years (1348.5 days) in AS, 4.5 years (1652.5 days) in AR and 4.1 years (1513 days) in MR. Figure 1B–D shows previous (i.e. prior to VHD diagnosis) and intervening (i.e. developed after VHD diagnosis, but before cardiac arrest) comorbidities. Hypertension was the most common condition prior to valvular diagnosis, being prevalent in 66% of patients who developed AS, 55% in AR and 56% in MR. Heart failure was more common prior to a diagnosis of MR (63%) and AR (42%) than AS (39%). Roughly one in five developed heart failure after being diagnosed with each respective valvular lesion. In all groups, the most common comorbidities developed after diagnosis of the valvular lesion were hypertension, heart failure, coronary artery disease and atrial fibrillation (Fig. 1B–D). Aortic aneurysm was roughly four times as common in patients with AR. Patients with MR had more atrial fibrillation and ischemic heart disease.

Cox adjusted survival curves from valvular diagnosis to cardiac arrest and coexisting and intervening conditions at valvular diagnosis. (A) Cox-adjusted survival curves for time from VHD to cardiac arrest. (B–D) Prior (i.e., to VHD diagnosis) and intervening (i.e., after VHD diagnosis) coexisting conditions. AS = aortic stenosis; AR = aortic regurgitation; MR = mitral regurgitation. Previous conditions is defined as comorbidities present prior to hospitalization for valvular disease. Intervening conditions refer to conditions developed after hospitalization for valvular disease, prior to cardiac arrest.

Baseline characteristics at cardiac arrest

Roughly one third of all patients in all groups were female (Table 1). The mean age at cardiac arrest was 80.3 years for patients with AS, 73.6 years for patients with AR, 75.6 years for patients with MR and 68.3 years for patients without valvular disease. Cardiovascular etiologies were the underlying causes in 83.0% of patients with AS, 82.7% in AR, 84.1% in MR and 61.2% in those without valvular disease. With regards to clock time, cardiac arrest was most common between 7 am to 12 am in all groups, with roughly one in three cases occurring during that time (Table 1 and Supplementary Fig. 1). The vast majority of all cases occurred at home, with small differences across the groups.

Median time from cardiac arrest to start of CPR was 3 min for AS, 3 min for AR, 3.5 min for MR and 3 min for those without valvular disease. Time to first defibrillation was 17 min for AS, 14 min for AR, 15.5 min for MR and 15 min for those without VHD. Time to EMS arrival was 12 min for AS, AR, MR and 13 min for those without VHD. Time to ROSC was 15, 13, 15, 15 min for AS, AR, MR, and those without VHD, respectively.

The initial rhythm was VF/pVT in 21.2% in AS, 26.7% in AR, 31.8% in MR, and 23.1% in patients without VHD. With regards to comorbidities (at the time of cardiac arrest) in patients with AS, 79.5% had hypertension, 60.2% had heart failure, 50.9% had chronic coronary artery disease, 49.0% had atrial fibrillation, 34.9% had diabetes, 35.8% had dyslipidemia.

Table 2 presents crude survival parameters. Return of spontaneous circulation (ROSC) at hospital arrival was observed in 34.6% of patients with AS, 41.7% in AR, 44.9% in MR and 45.1% in patients without VHD. Roughly 9% of patients with AS, AR and MR were conscious at hospital arrival, compared with 11% in patients without valvular disease (missing rate was high, as presented in Table 2). ROSC at any time occurred in 27.5% with AS, 33.3% with AR, 36.4% with MR and 34.7% in those without VHD. Survival at 30 days was 5.2% in AS, 10.4% in AR, 9.2% in MR and 11.4% in those without VHD. One-year survival was 3.9%, 8.1%, 8.1% and 10.2% in AS, AR, MR and no VHD, respectively.

Rates of ROSC, hospitalization and 30 days survival in relation to no-flow time

Figure 2 shows rates of ROSC, hospitalization and survival at 30 days in relation to no-flow time. Rates of ROSC, hospitalization and 30-days survival were clearly lower in people with AS compared to those without AS. ROSC rates declined from 40.1% when CPR was started in < 3 min to 20.0% when CPR was started in19-20 min in people without AS. Corresponding figures for those with AS were 29.4% and 8.9%, respectively. Survival rates for people with AS were very low throughout. For the majority (56%) of patients with AS, the delay to CPR was ≥ 3 min; survival was 1.2% to 3.9% in these patients. In patients where delay to EMS arrival was more than 11 min, survival was 11.5% in those without AS and 3.9% in those with AS when CPR was started in < 3 min. Supplementary Fig. 2 shows ROSC, hospitalization and survival rates in people with AS in relation to initial rhythm. As evident, there were virtually no survivors in people with AS presenting with asystole or PEA when no-flow time was longer than 10 min. Supplementary Figures 3 through 6 shows corresponding figures for AR and MR.

Rates of ROSC, hospitalization and 30 days survival in relation to aortic stenosis status. Crude rates of ROSC, hospitalization and 30-days survival in patients with AS and those with no VHD.

Short- and long-term survival after cardiac arrest

Short- and long-term survival was highest for patients without VHD (Fig. 3A). Survival dropped to around 10% for AR and MR within the first few days, but thereafter survival tended to be higher in those with AR. All 17 patients with MS died on the first day. Patients with AS had the poorest survival among the other left-sided valvular lesions. Figure 3B shows Kaplan–Meier curves for patients with AS in relation to age.

Kaplan Meier curves for survival from cardiac arrest. Kaplan–Meier curves describing short- and long-term survival stratified by (a) VHD status and (b) age-group in patients with AS. Note that y-axes are truncated.

Neurological outcomes (cerebral performance)

Figure 4A–B shows CPC scores among survivors. CPC score 1 (no neurological sequalae) was observed in 72.0% of patients with AS, 88.9% of patients with AR, 70.0% of patients with MR and 75.7% of patients with no valvular disease. Odds ratios, adjusted for age and sex, for surviving with CPC score 1, did not differ in AS, AR nor MR (all compared with no VHD). In patients of age 61–70 years with AS, no survivor had CPC score worse than 2.

Cerebral performance category score. Distribution of CPC score in relation to (A) VHD status and (B) age-group in patients with AS. Odds ratios are adjusted for age and sex.

Adjusted probability of survival

Figure 5A–D shows probability of survival overall in each valvular group and in 18 subgroups respectively (Fig. 5B–D).

A–D Adjusted probability of survival overall and in subgroups. AS = Aortic stenosis. AR = Aortic regurgitation. MR = Mitral regurgitation. Logistic regression for 30-days survival in the (A) overall cohort and subgroups (B–D). Models in (B–D) were adjusted for age, sex, initial rhythm, location, and no-flow time.

Overall odds ratios (Fig. 5A) were sequentially adjusted. As compared with no VHD, those with MR and AR showed no statistically significant difference in survival, while patients with AS displayed odds ratios of 0.57 in model 1 (95% CI 0.46–0.70), 0.57 in model 2 (95% CI 0.46–0.69) and 0.58 in model 3 (95% CI 0.46–0.72).

The association between AS (Fig. 5B) and 30-days survival was not significantly modified by age, sex, witnessed status, or coexisting conditions. However, the lowest odds ratio (judging the point estimates) of survival was noted in the subgroup of patients presenting with PEA, who displayed an odds ratio of 0.34 (95% CI 0.14–0.67).

With regards to AR, no subgroup displayed any significant difference in 30 days survival, although confidence intervals were wide (Fig. 5C).

For MR (Fig. 5D), the majority of all point estimates were below 1.0, suggesting a lower probability of survival. While in the overall analysis, there was no difference in survival between MR and no VHD, we note that for patients aged ≥ 65 years, those with cardiac etiology, VF/pVT, and patients with atrial fibrillation, survival was worse (~ 30% lower probability) in patients with MR, compared to no VHD.

Relative importance of predictors of survival

There were no significant differences with regards to determinants of survival in AS, AR and MR (Supplementary Fig. 7).