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Zimmermann et al. Vessel Plus 2019;3:31 I http://dx.doi.org/10.20517/2574-1209.2019.010 Page 11 of 18

to an extremely high procedural success rate (98%) [23,107] . Furthermore, Nakagawa et al. [103] reported that
after intervention in a population composed of patients 70 years or older with hemodynamically significant
ASD, percutaneous closure is efficacious and safe. The intervention led to a significant improvement of PA
pressure and NYHA functional class, as well as reversal of RV enlargement [103] .

Similarly, in 2014 Komar et al. [108] studied the mid-term outcome of patients over the age of 60.
Interestingly, their primary outcome was focused more on quality of life indices and functional benefits
rather than complications or long term survival. Metrics such as time of sustained exercise before feeling
short of breath, VO max, and the SF-36 quality of life questionnaire to gauge the benefits of ASD closure.
2
Symptomatic parameters like incidence of shortness of breath or time of exercise before shortness of
breath both improved significantly; furthermore 88% of patients surveyed had a significant subjective
improvement in quality of life 12 months following their index surgery [108] .

Obstacles in transcatheter atrial septal defect closure in elderly patients:
The most salient issue in elderly cases is not their primary pathology, but their co-morbid systemic
and cardiac diseases. This necessitates careful preoperative evaluation of the associated risk factors as
an essential aspect of successful treatment. Approximately one third of the patients showed systemic
hypertension and systemic diseases like diabetes mellitus, and a considerable extent of pulmonary and
neurological disease conditions were also present [109] . Among the cardiac co-morbidities pulmonary
hypertension is reported in nearly 50 % of the cases, chronic atrial arrhythmia in more than 20% and
ischemic heart disease in about 15% of the patients [110,111] . Post-closure pulmonary edema developed
because of “masked LV restriction” may appear in 2% to 4% of the elderly cases may be evaluated with a
balloon occlusion prior to ASD closure [112] .

Similarly, diastolic dysfunction and stiffening of the LV causes increased left to right shunting, which may
explain in part why the late diagnosis is established in elderly patients who were previously asymptomatic.
Careful assessment of left ventricular and left atrial pressures via left heart catheterization during
defect balloon occlusion and weighing potential hemodynamic consequences vs. perceived benefits of
intervention, are especially important in the elderly patient population. Miranda et al report that left
ventricular end diastolic pressure may help predict left atrial pressures in those undergoing ASD repair.
They found that the vast majority of patients who had a baseline left ventricular end diastolic pressure > 15 mmHg
developed significantly elevated left atrial pressure during balloon occlusion of ASD [113] .

ASD and pulmonary arterial hypertension
Due to chronic right ventricular volume overload, elderly patients with hemodynamically significant ASDs
have a tendency to present with pulmonary hypertension. Pulmonary hypertension develops as a result of
increased pulmonary blood flow due to left-to-right shunting. However, the anomalous rise in pulmonary
blood flow creates secondary physiologic changes such as pulmonary vascular intimal proliferation and
medial hypertrophy that affect pulmonary vascular resistance [114,115] . The consequence of such changes
has been observed to be reversible in younger patients, but may not be fully reversible in the elderly [116] .
It is well understood that the natural course of ASD and the associated effect on pulmonary hypertension
is notably worse than in patients without pulmonary hypertension [117] . Thus, pulmonary hypertension is
traditionally considered an absolute contraindication to ASD intervention, especially surgical closure [118] .
The expansion of therapeutic options for treating pulmonary hypertension may offer new avenues for
ASD closure. An area of active research is the role of ASD closure in combination with new pulmonary
hypertension treatments such as prostanoids, endothelin receptor antagonists, and phosphodiesterase-5
inhibitors, even if initial hemodynamic parameters are unamenable to ASD closure [119-122] . More recent
studies such as the North American Atrial Septal Defect Pulmonary Hypertension (NAAPH) Study
demonstrate feasibility of ASD closure in patients with PAH with an aggressive “treat to repair” strategy