Maniar, Hersh S.

Background Left ventricular aneurysm (LVA) is a significant complication of myocardial infarction that may lead to global left ventricular (LV) dysfunction. However, the exact mechanism underlying the abnormal function has not been elucidated. In this study we tested the hypothesis that changes in LV geometry cause both an increase in wall stress and a change in the temporal distribution of stress in the LVA border zone (BZ) during systole. Methods Transmural anteroapical infarcts were created in adult Dorsett sheep (n=8) and were allowed to mature into LVAs for 10 weeks. Animals were imaged subsequently using MRI with simultaneous recording of intraventricular pressures. Cardiac models were constructed from the MRI images at end-diastole, isovolumic systole, peak-systole and end-systole. Two short-axis slices, 1 basal and 1 apical were analyzed. The apical slice included the septal and anterior component of the aneurysm as well as the corresponding BZs and normal myocardium. Regional wall stresses were calculated using finite element analysis and compared with stresses in corresponding regions from normal control sheep (n=7). Results In the LVA group, stress was significantly increased in the BZ at the end-diastolic, isovolumic, peak-systolic, and end-systolic instants ( P <0.001 for all). In addition the temporal distribution of stress was significantly altered with maximum stress occurring at peak instead of isovolumic systole. Conclusions Geometric changes in the LVA hearts increased wall stress and altered its temporal distribution in the BZ region. Correlation of this finding with the corresponding regional blood flow, oxygen consumption, and mechanical systolic performance may help elucidate the mechanism underlying the observed global LV dysfunction.

Introduction: Pulmonary hypertension (PH) is associated with increased mortality after surgical or transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS). Hypothesis: We hypothesized that clinical or hemodynamic factors might influence the relationship between significant PH and increased mortality. Methods: Among patients with symptomatic AS at high or prohibitive surgical risk receiving TAVR in the PARTNER I randomized trial or registry, 2180 patients with an invasive measurement of mean pulmonary artery pressure (mPAP) recorded were included. PH was defined as: none (mPAP<25 mmHg), mild (25 to <35), and mod/sev (≥35). Results: One year all-cause mortality was worse with increasing severity of PH: none (n=785, 18.6%), mild (n=838, 22.7%), and mod/sev (n=557, 25.0%) (p=0.01). The association between mod/sev PH (vs. no PH) and 1y mortality varied by sex and renal function (interaction p=0.03 and p=0.06, respectively). In females, mod/sev PH was associated with increased mortality (24.6% vs. 14.1%, HR 1.89, 95% CI 1.32-2.73); in males it was not (24.9% vs. 22.2%, HR 1.12, 95% CI 0.82-1.52). Additionally, mod/sev PH was associated with mortality in those with glomerular filtration rate (GFR) <40 (HR 1.76, 95% CI 1.28-2.42), but not in those with GFR ≥40. In a multivariable Cox PH model of patients with mod/sev PH, oxygen dependent lung disease, cerebrovascular disease, lower GFR, and lower baseline transvalvular mean gradient were each independently associated with increased 1y mortality (p<0.05 for all), whereas pulmonary artery compliance was the only hemodynamic variable associated with mortality (p=0.043) (Table). Conclusions: The relationship between mod/sev PH and increased mortality after TAVR is altered by sex and renal function. While lower pulmonary artery compliance is associated with increased mortality in patients with significant PH, clinical factors appear to be more influential in stratifying risk than hemodynamic indices.

Objective Pulmonary hypertension (PH) is associated with increased mortality after surgical or transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS), and when the pulmonary artery pressure is particularly elevated, there may be questions about the clinical benefit of TAVR. We aimed to identify clinical and haemodynamic factors associated with increased mortality after TAVR among those with moderate/severe PH. Methods Among patients with symptomatic AS at high or prohibitive surgical risk receiving TAVR in the Placement of Aortic Transcatheter Valves (PARTNER) I randomised trial or registry, 2180 patients with an invasive measurement of mean pulmonary artery pressure (mPAP) recorded were included, and moderate/severe PH was defined as an mPAP ≥35 mm Hg. Results Increasing severity of PH was associated with progressively worse 1-year all-cause mortality: none (n=785, 18.6%), mild (n=838, 22.7%) and moderate/severe (n=557, 25.0%) (p=0.01). The increased hazard of mortality associated with moderate/severe PH was observed in females, but not males (interaction p=0.03). In adjusted analyses, females with moderate/severe PH had an increased hazard of death at 1 year compared with females without PH (adjusted HR 2.14, 95% CI 1.44 to 3.18), whereas those with mild PH did not. Among males, there was no increased hazard of death associated with any severity of PH. In a multivariable Cox model of patients with moderate/severe PH, oxygen-dependent lung disease, inability to perform a 6 min walk, impaired renal function and lower aortic valve mean gradient were independently associated with increased 1-year mortality (p<0.05 for all), whereas several haemodynamic indices were not. A risk score, including these factors, was able to identify patients with a 15% vs 59% 1-year mortality. Conclusions The relationship between moderate/severe PH and increased mortality after TAVR is altered by sex, and clinical factors appear to be more influential in stratifying risk than haemodynamic indices. These findings may have implications for the evaluation of and treatment decisions for patients referred for TAVR with significant PH. Trial registration NCT00530894.

Background— Tricuspid regurgitation (TR) and right ventricular (RV) dysfunction adversely affect outcomes in patients with heart failure or mitral valve disease, but their impact on outcomes in patients with aortic stenosis treated with transcatheter aortic valve replacement has not been well characterized. Methods and Results— Among 542 patients with symptomatic aortic stenosis treated in the Placement of Aortic Transcatheter Valves (PARTNER) II trial (inoperable cohort) with a Sapien or Sapien XT valve via a transfemoral approach, baseline TR severity, right atrial and RV size and RV function were evaluated by echocardiography according to established guidelines. One-year mortality was 16.9%, 17.2%, 32.6%, and 61.1% for patients with no/trace (n=167), mild (n=205), moderate (n=117), and severe (n=18) TR, respectively ( P <0.001). Increasing severity of RV dysfunction as well as right atrial and RV enlargement were also associated with increased mortality ( P <0.001). After multivariable adjustment, severe TR (hazard ratio, 3.20; 95% confidence interval, 1.50–6.82; P =0.003) and moderate TR (hazard ratio, 1.60; 95% confidence interval, 1.02–2.52; P =0.042) remained associated with increased mortality as did right atrial and RV enlargement, but not RV dysfunction. There was an interaction between TR and mitral regurgitation severity ( P =0.04); the increased hazard of death associated with moderate/severe TR only occurred in those with no/trace/mild mitral regurgitation. Conclusions— In inoperable patients treated with transcatheter aortic valve replacement, moderate or severe TR and right heart enlargement are independently associated with increased 1-year mortality; however, the association between moderate or severe TR and an increased hazard of death was only found in those with minimal mitral regurgitation at baseline. These findings may improve our assessment of anticipated benefit from transcatheter aortic valve replacement and support the need for future studies on TR and the right heart, including whether concomitant treatment of TR in operable but high-risk patients with aortic stenosis is warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01314313.