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Purpose of Review : This review summarizes the pathophysiology of calcific aortic valve stenosis (CAVS) and surveys relevant clinical data and basic research that explain how CAVS arises. Recent Findings : Lipoprotein(a) [Lp(a)], lipoprotein-associated phospholipase A2 (Lp-PLA2), oxidized phospholipids (OxPL), autotaxin, and genetic driving forces such as mutations in LPA gene and NOTCH gene seem to play a major role in the development of CAVS. These factors might well become targets of medical therapy in the coming years. Summary : CVAS seems to be a multifactorial disease that has much in common with coronary artery disease, mainly regarding lipidic accumulation and calcium deposition. No clinical trials conducted to date have managed to answer the key question of whether Lp(a) lowering and anti-calcific therapies confer a benefit in terms of reducing incidence or progression of CAVS, although additional outcome trials are ongoing.

OBJECTIVES: This study sought to evaluate the impact of patient–prosthesis mismatch (PPM) on the risk of perioperative, early-, mid- and long-term mortality rates after surgical aortic valve replacement. METHODS: Databases were searched for studies published until March 2018. The main outcomes of interest were perioperative mortality, 1-year mortality, 5-year mortality and 10-year mortality. RESULTS: The search yielded 3761 studies for inclusion. Of these, 70 articles were analysed, and their data were extracted. The total num- ber of patients included was 108 182 who underwent surgical aortic valve replacement. The incidence of PPM after surgical aortic valve re- placement was 53.7% (58 116 with PPM and 50 066 without PPM). Perioperative mortality [odds ratio (OR) 1.491, 95% confidence interval (CI) 1.302–1.707; P < 0.001], 1-year mortality (OR 1.465, 95% CI 1.277–1.681; P < 0.001), 5-year mortality (OR 1.358, 95% CI 1.218–1.515; P < 0.001) and 10-year mortality (OR 1.534, 95% CI 1.290–1.825; P < 0.001) were increased in patients with PPM. Both severe PPM and moderate PPM were associated with increased risk of perioperative mortality, 1-year mortality, 5-year mortality and 10-year mortality when analysed together and separately, although we observed a higher risk in the group with severe PPM. CONCLUSIONS: Moderate/severe PPM increases perioperative, early-, mid- and long-term mortality rates proportionally to its severity. The findings of this study support the implementation of surgical strategies to prevent PPM in order to decrease mortality rates.

OBJECTIVES: This study sought to evaluate the impact of surgical aortic root enlargement (ARE) on the perioperative outcomes of aortic valve replacement (AVR). METHODS: Databases were searched for studies published until April 2018 to carry out a systematic review followed by meta-analysis of results. RESULTS: The search yielded 1468 studies for inclusion. Of these, 10 articles were analysed and their data extracted. A total of 13 174 patients (AVR with ARE: 2819 patients; AVR without ARE: 10 355 patients) were included from studies published from 2002 to 2018. The total rate of ARE was 21.4%, varying in the studies from 5.7% to 26.3%. The overall odds ratio (OR) [95% confidence interval (CI)] for periop- erative mortality showed a statistically significant difference between the groups (among 10 studies), with a higher risk in the ‘AVR with ARE’ group (OR 1.506, 95% CI 1.209–1.875; P < 0.001), but not when adjusted for isolated AVR + ARE without any concomitant procedures such as mitral valve surgery, coronary artery bypass surgery, etc. (OR 1.625, 95% CI 0.968–2.726; P = 0.066—among 6 studies). The ‘AVR with ARE’ group showed an overall lower risk of significant patient–prosthesis mismatch among 9 studies (OR 0.472, 95% CI 0.295–0.756; P = 0.002) and a higher overall difference in means of indexed effective orifice area among 10 studies (random-effect model: 0.06 cm2/m2, 95% CI 0.029–0.103; P < 0.001). CONCLUSIONS: Surgical ARE seems to be associated with increased perioperative mortality but with lower risk of patient–prosthesis mismatch.

Objective: This study sought to evaluate the impact of prosthesis-patient mismatch on the risk of perioperative and long- term mortality after mitral valve replacement. Methods: Databases were researched for studies published until December 2018. Main outcomes of interest were perioperative and 10-year mortality and echocardiographic parameters. Results: The research yielded 2,985 studies for inclusion. Of these, 16 articles were analyzed, and their data extracted. The total number of patients included was 10,239, who underwent mitral valve replacement. The incidence of prosthesis-patient mismatch after mitral valve replacement was 53.7% (5,499 with prosthesis- patient mismatch and 4,740 without prosthesis-patient mismatch). Perioperative (OR 1.519; 95%CI 1.194–1.931, P<0.001) and 10-year (OR 1.515; 95%CI 1.280–1.795, P<0.001) mortality was increased in patients with prosthesis-patient mismatch. Patients with prosthesis-patient mismatch after mitral valve replacement had higher systolic pulmonary artery pressure and transprosthethic gradient and lower indexed effective orifice area and left ventricle ejection fraction. Conclusion: Prosthesis-patient mismatch increases perioperative and long-term mortality. Prosthesis-patient mismatch is also associated with pulmonary hypertension and depressed left ventricle systolic function. The findings of this study support the implementation of surgical strategies to prevent prosthesis- patient mismatch in order to decrease mortality rates.

Purpose of Review : This review summarizes the pathophysiology of calcific aortic valve stenosis (CAVS) and surveys relevant clinical data and basic research that explain how CAVS arises. Recent Findings : Lipoprotein(a) [Lp(a)], lipoprotein-associated phospholipase A2 (Lp-PLA2), oxidized phospholipids (OxPL), autotaxin, and genetic driving forces such as mutations in LPA gene and NOTCH gene seem to play a major role in the development of CAVS. These factors might well become targets of medical therapy in the coming years. Summary : CVAS seems to be a multifactorial disease that has much in common with coronary artery disease, mainly regarding lipidic accumulation and calcium deposition. No clinical trials conducted to date have managed to answer the key question of whether Lp(a) lowering and anti-calcific therapies confer a benefit in terms of reducing incidence or progression of CAVS, although additional outcome trials are ongoing.

OBJECTIVES: This study sought to evaluate the impact of surgical aortic root enlargement (ARE) on the perioperative outcomes of aortic valve replacement (AVR). METHODS: Databases were searched for studies published until April 2018 to carry out a systematic review followed by meta-analysis of results. RESULTS: The search yielded 1468 studies for inclusion. Of these, 10 articles were analysed and their data extracted. A total of 13 174 patients (AVR with ARE: 2819 patients; AVR without ARE: 10 355 patients) were included from studies published from 2002 to 2018. The total rate of ARE was 21.4%, varying in the studies from 5.7% to 26.3%. The overall odds ratio (OR) [95% confidence interval (CI)] for periop- erative mortality showed a statistically significant difference between the groups (among 10 studies), with a higher risk in the ‘AVR with ARE’ group (OR 1.506, 95% CI 1.209–1.875; P < 0.001), but not when adjusted for isolated AVR + ARE without any concomitant procedures such as mitral valve surgery, coronary artery bypass surgery, etc. (OR 1.625, 95% CI 0.968–2.726; P = 0.066—among 6 studies). The ‘AVR with ARE’ group showed an overall lower risk of significant patient–prosthesis mismatch among 9 studies (OR 0.472, 95% CI 0.295–0.756; P = 0.002) and a higher overall difference in means of indexed effective orifice area among 10 studies (random-effect model: 0.06 cm2/m2, 95% CI 0.029–0.103; P < 0.001). CONCLUSIONS: Surgical ARE seems to be associated with increased perioperative mortality but with lower risk of patient–prosthesis mismatch.

Objective: This study sought to evaluate the impact of prosthesis-patient mismatch on the risk of perioperative and long- term mortality after mitral valve replacement. Methods: Databases were researched for studies published until December 2018. Main outcomes of interest were perioperative and 10-year mortality and echocardiographic parameters. Results: The research yielded 2,985 studies for inclusion. Of these, 16 articles were analyzed, and their data extracted. The total number of patients included was 10,239, who underwent mitral valve replacement. The incidence of prosthesis-patient mismatch after mitral valve replacement was 53.7% (5,499 with prosthesis- patient mismatch and 4,740 without prosthesis-patient mismatch). Perioperative (OR 1.519; 95%CI 1.194–1.931, P<0.001) and 10-year (OR 1.515; 95%CI 1.280–1.795, P<0.001) mortality was increased in patients with prosthesis-patient mismatch. Patients with prosthesis-patient mismatch after mitral valve replacement had higher systolic pulmonary artery pressure and transprosthethic gradient and lower indexed effective orifice area and left ventricle ejection fraction. Conclusion: Prosthesis-patient mismatch increases perioperative and long-term mortality. Prosthesis-patient mismatch is also associated with pulmonary hypertension and depressed left ventricle systolic function. The findings of this study support the implementation of surgical strategies to prevent prosthesis- patient mismatch in order to decrease mortality rates.

OBJECTIVES: This study sought to evaluate the impact of patient–prosthesis mismatch (PPM) on the risk of perioperative, early-, mid- and long-term mortality rates after surgical aortic valve replacement. METHODS: Databases were searched for studies published until March 2018. The main outcomes of interest were perioperative mortality, 1-year mortality, 5-year mortality and 10-year mortality. RESULTS: The search yielded 3761 studies for inclusion. Of these, 70 articles were analysed, and their data were extracted. The total num- ber of patients included was 108 182 who underwent surgical aortic valve replacement. The incidence of PPM after surgical aortic valve re- placement was 53.7% (58 116 with PPM and 50 066 without PPM). Perioperative mortality [odds ratio (OR) 1.491, 95% confidence interval (CI) 1.302–1.707; P < 0.001], 1-year mortality (OR 1.465, 95% CI 1.277–1.681; P < 0.001), 5-year mortality (OR 1.358, 95% CI 1.218–1.515; P < 0.001) and 10-year mortality (OR 1.534, 95% CI 1.290–1.825; P < 0.001) were increased in patients with PPM. Both severe PPM and moderate PPM were associated with increased risk of perioperative mortality, 1-year mortality, 5-year mortality and 10-year mortality when analysed together and separately, although we observed a higher risk in the group with severe PPM. CONCLUSIONS: Moderate/severe PPM increases perioperative, early-, mid- and long-term mortality rates proportionally to its severity. The findings of this study support the implementation of surgical strategies to prevent PPM in order to decrease mortality rates.