Gender Difference in Ventricular Response to Aortic Stenosis: Insight from Cardiovascular Magnetic Resonance

<div><p>Background</p><p>Although left ventricular hypertrophy (LVH) and remodeling is associated with cardiac mortality and morbidity, little is known about the impact of gender on the ventricular response in aortic stenosis (AS) patients. This study aimed to analyze the differential effect of gender on ventricular remodeling in moderate to severe AS patients.</p><p>Methods and Results</p><p>A total of 118 consecutive patients (67±9 years; 63 males) with moderate or severe AS (severe 81.4%) underwent transthoracic echocardiography and cardiovascular magnetic resonance (CMR) within a 1-month period in this two-center prospective registry. The pattern of LV remodeling was assessed using the LV mass index (LVMI) and LV remodeling index (LVRI; LV mass/LV end-diastolic volume) by CMR. Although there were no differences in AS severity parameters nor baseline characteristics between genders, males showed a significantly higher LVMI (102.6±29.1g/m² vs. 86.1±29.2g/m², p=0.003) and LVRI (1.1±0.2 vs. 1.0±0.3, p=0.018), regardless of AS severity. The LVMI was significantly associated with aortic valve area (AVA) index and valvuloarterial impedance in females, whereas it was not in males, resulting in significant interaction between genders (PInteraction=0.007/0.014 for AVA index/valvuloarterial impedance, respectively). Similarly, the LVRI also showed a significantly different association between male and female subjects with the change in AS severity parameters (PInteraction=0.033/<0.001/0.029 for AVA index/transaortic mean pressure gradient/valvuloarterial impedance, respectively).</p><p>Conclusion</p><p>Males are associated with greater degree of LVH and higher LVRI compared to females at moderate to severe AS. However, females showed a more exaggerated LV remodeling response, with increased severity of AS and hemodynamic loads, than males.</p></div

Echocardiographic and cardiovascular magnetic resonance (CMR) parameters of the study participants.

<p>The data are presented as mean (SD), except adjusted mean (SE) in the body mass index adjusted LV mass.</p><p>^†When quantifying the LV mass, the trabeculations and the papillary muscles were excluded.</p><p>Abbreviations: AR, aortic regurgitation; AS, aortic stenosis; AVA, aortic valve area; BMI, body mass index; BSA, body surface area; E, early diastolic velocity at the mitral valve tip; e’, early mitral annular velocity at the septal annulus; IVST, interventricular septal thickness; LV, left ventricle; PG, pressure gradient; PWT, posterior wall thickness; Vmax, maximal transaortic velocity; Z_VA, valvuloarterial impedance.</p><p>Echocardiographic and cardiovascular magnetic resonance (CMR) parameters of the study participants.</p

Additional file 1: Figure S1. of Pulmonary hemodynamics and effects of phosphodiesterase type 5 inhibition in heart failure: a meta-analysis of randomized trials

Quality assessment. (A) Risk of bias summary. (B) Risk of bias graph. (PPTX 76 kb

Baseline clinical characteristics of the study participants.

<p>The data are presented as mean (SD) or number (percentage).</p><p>Abbreviations: ACEI/ARB, angiotensin converting enzyme inhibitor/angiotensin receptor blocker; BMI, body mass index; HTN, hypertension; NYHA, New York Heart Association.</p><p>Baseline clinical characteristics of the study participants.</p

The association between left ventricular remodeling index and the severity of aortic stenosis or valvuloarterial impedance.

<p>Males consistently showed relatively higher left ventricular remodeling index in (A) larger aortic valve area index, (B) lower mean transaortic pressure gradient, or (C) lower valvuloarterial impedance, compared with females. However, there were significant differences between the two genders in the degree of correlation between the left ventricular remodeling index and the above three parameters. The univariate linear regression coefficient and the interaction p value across the gender are shown. Abbreviations: AV, aortic valve; AVA, aortic valve area; CMR, cardiovascular magnetic resonance; PG, pressure gradient.</p

Additional file 2: Figure S2. of Pulmonary hemodynamics and effects of phosphodiesterase type 5 inhibition in heart failure: a meta-analysis of randomized trials

Effect of PDE5i on BP and HR. Forest plot of the pooled weighted mean differences of (A) SBP (mmHg), (B) DBP (mmHg), (C) MAP (mmHg), and (D) HR (beat per minute). Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; HR, heart rate. Figure S3. Effect of PDE5i on cardiac performance. Forest plot of the pooled weighted mean differences of (A) cardiac index (L/min/m2), and (B) cardiac output (L/min). (TIF 5850 kb

Additional file 3: Figure S4. of Pulmonary hemodynamics and effects of phosphodiesterase type 5 inhibition in heart failure: a meta-analysis of randomized trials

Influence analysis for the RCTs of HFpEF. Sensitivity analysis was performed to assess the potential influence of each RCT to the effect size of the RCTs of HFpEF. Pooled effects of PDE5i when each RCT was omitted were shown for (A) LVEF (%), (B) mPAP (mmHg), (C) PASP (mmHg), and (D) PVR (dyn¡sec/cm5). The omission of the study by Guazzi M et al. [12] significantly changed the pooled effect size of PDE5i, suggesting that there was a substantial influence from the study by Guazzi M et al. on the overall outcome measures. Abbreviations: RCT, randomized controlled trial; HFpEF, heart failure with preserved ejection fraction; PDE5i, phosphodiesterase type 5 inhibitor; LVEF, left ventricular ejection fraction; mPAP, mean pulmonary artery pressure; PASP, pulmonary artery systolic pressure; PVR, pulmonary vascular resistance. (PPTX 588 kb

Additional file 2: of Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM): study protocol for a randomized controlled trial

Supplementary methods for details of imaging protocols. (DOCX 26 kb

Additional file 1: of Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM): study protocol for a randomized controlled trial

SPIRIT 2013 checklist: recommended items to address in a clinical trial protocol and related documents. (DOCX 48 kb

Baseline characteristics of total study population.

<p>Data are mean±SD, median (IQR; Q1–Q3) or number (%).</p><p>*Chronic kidney disease was defined as estimated glomerular filtration rate (GFR) <60 mL/min/1.73m².</p><p>^†Calculations of the laboratory tests and coronary artery calcium score were performed for those with available data of each component.</p><p>^‡A composite of all-cause mortality and late coronary revascularization (>90 days after CCTA), including percutaneous coronary intervention and coronary artery bypass graft operation.</p><p>Abbreviations: COPD, chronic obstructive pulmonary disease; ACEi, angiogensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; CCB, calcium channel blocker; HDL, high-density lipoprotein; LDL, low-density lipoprotein; hsCRP, high-sensitivity C-reactive protein; GFR, glomerular filtration rate; CACS, coronary artery calcium score; CCTA, coronary computed tomography angiography.</p><p>Baseline characteristics of total study population.</p