Extracellular Myocardial Volume in Patients With Aortic Stenosis.

BACKGROUND: Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis. OBJECTIVES: This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes. METHODS: Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery-based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters. RESULTS: Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p < 0.05 for all), the latter 2 associations being independent of all other clinical variables (p = 0.035 and p < 0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p = 0.009). Not only was ECV% associated with cardiovascular mortality (p = 0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% confidence interval [1.02 to 1.19]; p = 0.013). CONCLUSIONS: In patients with severe aortic stenosis scheduled for aortic valve intervention, an increased ECV% is a measure of left ventricular decompensation and a powerful independent predictor of mortality.

Sex differences in left ventricular remodelling, myocardial fibrosis and mortality after aortic valve replacement.

OBJECTIVES: To investigate sex differences in left ventricular remodelling and outcome in patients undergoing surgical or transcatheter aortic valve replacement (SAVR/TAVR). METHODS: In this multicentre, observational, outcome study with imaging core-lab analysis, patients with severe aortic stenosis (AS) listed for intervention at one of six UK centres were prospectively recruited and underwent cardiovascular magnetic resonance imaging. The primary endpoint was all-cause mortality and secondary endpoint was cardiovascular mortality. RESULTS: 674 patients (425 men, 249 women, age 75±14 years) were included: 399 SAVR, 275 TAVR. Women were older, had higher surgical risk scores and underwent TAVR more frequently (53% vs 33.6%, p<0.001). More men had bicuspid aortic valves (BAVs) (26.7% vs 14.9%, p<0.001) and demonstrated more advanced remodelling than women. During a median follow-up of 3.6 years, 145 (21.5%) patients died, with no significant sex difference in all-cause mortality (23.3% vs 20.5%, p=0.114), but higher cardiovascular mortality in women (13.7% vs 8.5%, p=0.012). There were no significant sex-related differences in outcome in the SAVR or TAVR subgroups, or after excluding those with BAV. Factors independently associated with all-cause mortality were age, left ventricular ejection fraction (LVEF), BAV (better) and myocardial fibrosis detected with late gadolinium enhancement (LGE) in men, and age, LVEF and LGE in women. Age and LGE were independently associated with cardiovascular mortality in both sexes. CONCLUSIONS: Men demonstrate more advanced remodelling in response to a similar severity of AS. The higher cardiovascular mortality observed in women following AVR is accounted for by women having less BAV and higher risk scores resulting in more TAVR. LGE is associated with a worse prognosis in both sexes.

Silent cerebral infarction and cognitive function following TAVI: an observational two-centre UK comparison of the first-generation CoreValve and second-generation Lotus valve.

OBJECTIVE: To compare the incidence of silent cerebral infarction and impact on cognitive function following transcatheter aortic valve implantation (TAVI) with the first-generation CoreValve (Medtronic, Minneapolis, Minnesota, USA) and second-generation Lotus valve (Boston Scientific, Natick Massachusetts, USA). DESIGN: A prospective observational study comprising a 1.5 T cerebral MRI scan, performed preoperatively and immediately following TAVI, and neurocognitive assessments performed at baseline, 30 days and 1 year follow-up. SETTING: University hospitals of Leeds and Leicester, UK. PATIENTS: 66 (80.6±8.0 years, 47% male) patients with high-risk severe symptomatic aortic stenosis recruited between April 2012 and May 2015. MAIN OUTCOME MEASURES: Incidence of new cerebral microinfarction and objective decline in neurocognitive performance. RESULTS: All underwent cerebral MRI at baseline and immediately following TAVI, and 49 (25 Lotus, 24 CoreValve) completed neurocognitive assessments at baseline, 30 days and 1 year. There was a significantly greater incidence of new cerebral microinfarction observed following the Lotus TAVI (23 (79%) vs 22 (59%), p=0.025) with a greater number of new infarcts per patient (median 3.5 (IQR 7.0) vs 2.0 (IQR 3.0), p=0.002). The mean volume of infarcted cerebral tissue per patient was equivalent following the two prostheses (p=0.166). More patients suffered new anterior (14 (48%) vs 2 (5%), p=0.001) and vertebrobasilar (15 (52%) vs 7 (19%), p=0.005) lesions following Lotus. Lotus was associated with a decline in verbal memory and psychomotor speed at 30 days. However, performance longitudinally at 1 year was preserved in all neurocognitive domains. CONCLUSIONS: There was a higher incidence of silent cerebral microinfarction and a greater number of lesions per patient following Lotus compared with CoreValve. However, there was no objective decline in neurocognitive function discernible at 1 year following TAVI with either prosthesis.

Cardiovascular magnetic resonance assessment of 1st generation CoreValve and 2nd generation Lotus valves.

OBJECTIVES: We sought to compare using serial CMR, the quantity of AR and associated valve hemodynamics, following the first-generation CoreValve (Medtronic, Minneapolis, MN) and the second-generation Lotus valve (Boston Scientific, Natick, MA). BACKGROUND: Aortic regurgitation (AR) following Transcatheter Aortic Valve Replacement (TAVR) confers a worse prognosis and can be accurately quantified using cardiovascular magnetic resonance (CMR). Second generation valves have been specifically designed to reduce paravalvular AR and improve clinical outcomes. METHODS: Fifty-one patients (79.0 ± 7.7 years, 57% male) were recruited and imaged at three time points: immediately pre- and post-TAVR, and at 6 months. RESULTS: CMR-derived AR fraction immediately post-TAVR was greater in the CoreValve compared to Lotus group (11.7 ± 8.4 vs. 4.3 ± 3.4%, P = 0.001), as was the frequency of ≥moderate AR (9/24 (37.5%) versus 0/27, P < 0.001). However, at 6 months AR fraction had improved significantly in the CoreValve group such that the two valve designs were comparable (6.4 ± 5.0 vs 5.6 ± 5.3%, P = 0.623), with no patient in either group having ≥moderate AR. The residual peak pressure gradient immediately following TAVR was significantly lower with CoreValve compared to Lotus (14.1 ± 5.6 vs 25.4 ± 11.6 mmHg, P = 0.001), but again by 6 months the two valve designs were comparable (16.5 ± 9.4 vs 19.7 ± 10.5 mmHg, P = 0.332). There was no difference in the degree of LV reverse remodeling between the two valves at 6 months. CONCLUSION: Immediately post-TAVR, there was significantly less AR but a higher residual peak pressure gradient with the Lotus valve compared to CoreValve. However, at 6 months both devices had comparable valve hemodynamics and LV reverse remodeling.

Quantitative deformation analysis differentiates ischaemic and non-ischaemic cardiomyopathy: sub-group analysis of the VINDICATE trial.

Aims: To test the hypothesis that patients with ischaemic cardiomyopathy (ICM) and non-ischaemic cardiomyopathy (NICM) have different torsion and strain parameters, and compare to healthy, age-matched controls. VINDICATE investigated efficacy of high-dose vitamin D on patients with heart failure (HF) secondary to left ventricular (LV) systolic dysfunction of any aetiology. It is important to differentiate ICM and NICM as treatment and prognosis varies significantly. Cardiovascular magnetic resonance (CMR) reliably determines aetiology of HF and tissue tagging techniques are recognized as the reference standard measures of strain and torsion. Methods and results: Fifty three patients (31 ICM, 22 NICM) from VINDICATE and 25 controls underwent CMR at 3.0T, including cine imaging in multiple planes and tissue tagging by spatial modulation of magnetization. CMR data were analysed blinded, by quantitatively reporting circumferential strain and torsion from tagged images and global longitudinal strain from feature tracking. HF patients had larger ventricles indexed to body surface area, lower left ventricular ejection fraction (LVEF), LV torsion, twist, and strain parameters compared to controls. There were no significant differences between ICM and NICM in age, blood pressure, heart rhythm, or NYHA status. There was no significant difference in LV dimensions, EF, and strain parameters between ICM and NICM. NICM patients had significantly lower LV twist (6.0 ± 3.7° vs. 8.8 ± 4.3°, P = 0.023) and torsion (5.9 ± 3.5° vs. 8.8 ± 4.7°, P = 0.017) compared to ICM. Conclusion: Twist, torsion, and strain are reduced in HF patients compared to controls. Torsion and twist are significantly lower in patients with NICM compared to ICM, despite similar volumetric dimensions, circumferential and longitudinal strain parameters, and LVEF.

Mechanical Circulatory Support for Decompensated Heart Failure.

PURPOSE OF REVIEW: Cardiogenic shock from decompensated heart failure is associated with significant morbidity and mortality. Mechanical circulatory support (MCS) improves haemodynamics and reverses organ dysfunction in critically ill patients with cardiogenic shock. This paper summarises the main modalities of mechanical support and their physiological impact, practical considerations, advantages and disadvantages to facilitate a holistic approach in managing a potentially lethal pathology. RECENT FINDINGS: To date, there remains a lack of large randomised controlled trials to support the use of any mechanical support strategy. Consequently, meta-analyses, registry data and expert consensus in the form of society guidelines are relied upon. Currently, randomised trials are in progress to assess the efficacy of a percutaneous assist device (Impella) and extracorporeal membrane oxygenation. Mechanical support options are centred around the use of counter pulsation and percutaneous assist devices and the use of an extracorporeal pump and are hence varied in means of application, degree of haemodynamic benefit and potential complications. Regardless of future innovations, a timely multidisciplinary approach that incorporates both patient and institutional considerations will always be crucial to a successful outcome.

Cardiovascular magnetic resonance evaluation of symptomatic severe aortic stenosis: association of circumferential myocardial strain and mortality.

BACKGROUND: It is unknown whether circumferential strain is associated with prognosis after treatment of aortic stenosis (AS). We aimed to characterise strain in severe AS, using myocardial tagging cardiovascular magnetic resonance (CMR), prior to and following Transcatheter Aortic Valve Implantation (TAVI) and Surgical Aortic Valve Replacement (SAVR), and determine whether abnormalities in strain were associated with outcome. METHODS: CMR was performed pre- and 6 m post-intervention in 98 patients (52 TAVI, 46 SAVR; 77 ± 8 years) with severe AS. TAVI patients were older (80.9 ± 6.4 vs. 73.0 ± 7.0 years, p < 0.01) with a higher STS score (2.06 ± 0.6 vs. 6.03 ± 3.4, p < 0.001). Tagged cine images were acquired at the basal, mid and apical LV levels with a complementary spatial modulation of magnetization (CSPAMM) pulse sequence. Circumferential strain, strain rate and rotation were calculated using inTag© software. RESULTS: No significant change in basal or mid LV circumferential strain, or of diastolic strain rate, was seen following either intervention. However, a significant and comparable decline in LV torsion and twist was observed (SAVR: torsion 14.08 ± 8.40 vs. 7.81 ± 4.51, p < 0.001, twist 16.17 ± 7.01 vs.12.45 ± 4.78, p < 0.01; TAVI: torsion 14.43 ± 4.66 vs. 11.20 ± 4.62, p < 0.001, twist 16.08 ± 5.36 vs. 12.36 ± 5.21, p < 0.001) which likely reflects an improvement towards normal physiology following relief of AS. Over a maximum 6.0y follow up, there were 23 (16%) deaths following valve intervention. On multivariable Cox analysis, baseline mid LV circumferential strain was significantly associated with all-cause mortality (hazard ratio, 1.03; 1.01-1.05; p = 0.009) independent of age, LV ejection fraction and STS mortality risk score. ROC analysis indicated a mid LV circumferential strain > -18.7% was associated with significantly reduced survival. CONCLUSION: TAVI and SAVR procedures are associated with comparable declines in rotational LV mechanics at 6 m, with largely unchanged strain and strain rates. Pre-operative peak mid LV circumferential strain is associated with post-operative mortality.

Myocardial Extracellular Volume Estimation by CMR Predicts Functional Recovery Following Acute MI.

OBJECTIVES: In the setting of reperfused acute myocardial infarction (AMI), the authors sought to compare prediction of contractile recovery by infarct extracellular volume (ECV), as measured by T1-mapping cardiac magnetic resonance (CMR), with late gadolinium enhancement (LGE) transmural extent. BACKGROUND: The transmural extent of myocardial infarction as assessed by LGE CMR is a strong predictor of functional recovery, but accuracy of the technique may be reduced in AMI. ECV mapping by CMR can provide a continuous measure associated with the severity of tissue damage within infarcted myocardium. METHODS: Thirty-nine patients underwent acute (day 2) and convalescent (3 months) CMR scans following AMI. Cine imaging, tissue tagging, T2-weighted imaging, modified Look-Locker inversion T1 mapping natively and 15 min post-gadolinium-contrast administration, and LGE imaging were performed. The ability of acute infarct ECV and acute transmural extent of LGE to predict convalescent wall motion, ejection fraction (EF), and strain were compared per-segment and per-patient. RESULTS: Per-segment, acute ECV and LGE transmural extent were associated with convalescent wall motion score (p < 0.01; p < 0.01, respectively). ECV had higher accuracy than LGE extent to predict improved wall motion (area under receiver-operating characteristics curve 0.77 vs. 0.66; p = 0.02). Infarct ECV ≤0.5 had sensitivity 81% and specificity 65% for prediction of improvement in segmental function; LGE transmural extent ≤0.5 had sensitivity 61% and specificity 71%. Per-patient, ECV and LGE correlated with convalescent wall motion score (r = 0.45; p < 0.01; r = 0.41; p = 0.02, respectively) and convalescent EF (p < 0.01; p = 0.04). ECV and LGE extent were not significantly correlated (r = 0.34; p = 0.07). In multivariable linear regression analysis, acute infarct ECV was independently associated with convalescent infarct strain and EF (p = 0.03; p = 0.04), whereas LGE was not (p = 0.29; p = 0.24). CONCLUSIONS: Acute infarct ECV in reperfused AMI can complement LGE assessment as an additional predictor of regional and global LV functional recovery that is independent of transmural extent of infarction.

Right ventricular function following surgical aortic valve replacement and transcatheter aortic valve implantation: A cardiovascular MR study.

OBJECTIVE: The response of the RV following treatment of aortic stenosis is poorly defined, reflecting the challenge of accurate RV assessment. Cardiovascular magnetic resonance (CMR) is the established reference for imaging of RV volumes, mass and function. We sought to define the impact of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) upon RV function in patients treated for severe aortic stenosis using CMR. METHODS: A 1.5T CMR scan was performed preoperatively and 6months postoperatively in 112 (56 TAVI, 56 SAVR; 76±8years) high-risk severe symptomatic aortic stenosis patients across two UK cardiothoracic centres. RESULTS: TAVI patients were older (80.4±6.7 vs. 72.8±7.2years, p<0.05) with a higher STS score (2.13±0.73 vs. 5.54±3.41%, p<0.001). At 6months, SAVR was associated with a significant increase in RV end systolic volume (33±10 vs. 37±10ml/m2, p=0.008), and decrease in RV ejection fraction (58±8 vs. 53±8%, p=0.005) and tricuspid annular plane systolic excursion (22±5 vs. 14±3mm, p<0.001). Only 4 (7%) SAVR patients had new RV late gadolinium hyper-enhancement with no new cases seen in the TAVI patients at 6months. Longer surgical cross-clamp time was the only predictor of increased RV end systolic volume at 6months. Post-TAVI, there was no observed change in RV volumes or function. Over a maximum 6.3year follow-up, 18(32%) of TAVI patients and 1(1.7%) of SAVR patients had died (p=0.001). On multivariable Cox analysis, the RV mass at 6m post-TAVI was independently associated with all-cause mortality (HR 1.359, 95% CI 1.108-1.666, p=0.003). CONCLUSIONS: SAVR results in a deterioration in RV systolic volumes and function associated with longer cross-clamp times and is not fully explained by suboptimal RV protection during cardiopulmonary bypass. TAVI had no adverse impact upon RV volumes or function.

The role of cardiovascular magnetic resonance in the assessment of severe aortic stenosis and in post-procedural evaluation following transcatheter aortic valve implantation and surgical aortic valve replacement.

Degenerative aortic stenosis (AS) is the most common valvular disease in the western world with a prevalence expected to double within the next 50 years. International guidelines advocate the use of cardiovascular magnetic resonance (CMR) as an investigative tool, both to guide diagnosis and to direct optimal treatment. CMR is the reference standard for quantifying both left and right ventricular volumes and mass, which is essential to assess the impact of AS upon global cardiac function. Given the ability to image any structure in any plane, CMR offers many other diagnostic strengths including full visualisation of valvular morphology, direct planimetry of orifice area, the quantification of stenotic jets and in particular, accurate quantification of valvular regurgitation. In addition, CMR permits reliable and accurate measurements of the aortic root and arch which can be fundamental to appropriate patient management. There is a growing evidence base to indicate tissue characterisation using CMR provides prognostic information, both in asymptomatic AS patients and those undergoing intervention. Furthermore, a number of current clinical trials will likely raise the importance of CMR in routine patient management. This article will focus on the incremental value of CMR in the assessment of severe AS and the insights it offers following valve replacement.

Assessment of aortic stiffness by cardiovascular magnetic resonance following the treatment of severe aortic stenosis by TAVI and surgical AVR.

BACKGROUND: Aortic stiffness is increasingly used as an independent predictor of adverse cardiovascular outcomes. We sought to compare the impact of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) upon aortic vascular function using cardiovascular magnetic resonance (CMR) measurements of aortic distensibility and pulse wave velocity (PWV). METHODS AND RESULTS: A 1.5 T CMR scan was performed pre-operatively and at 6 m post-intervention in 72 patients (32 TAVI, 40 SAVR; age 76 ± 8 years) with high-risk symptomatic severe aortic stenosis. Distensibility of the ascending and descending thoracic aorta and aortic pulse wave velocity were determined at both time points. TAVI and SAVR patients were comparable for gender, blood pressure and left ventricular ejection fraction. The TAVI group were older (81 ± 6.3 vs. 72.8 ± 7.0 years, p < 0.05) with a higher EuroSCORE II (5.7 ± 5.6 vs. 1.5 ± 1.0 %, p < 0.05). At 6 m, SAVR was associated with a significant decrease in distensibility of the ascending aorta (1.95 ± 1.15 vs. 1.57 ± 0.68 × 10(-3)mmHg(-1), p = 0.044) and of the descending thoracic aorta (3.05 ± 1.12 vs. 2.66 ± 1.00 × 10(-3)mmHg(-1), p = 0.018), with a significant increase in PWV (6.38 ± 4.47 vs. 11.01 ± 5.75 ms(-1), p = 0.001). Following TAVI, there was no change in distensibility of the ascending aorta (1.96 ± 1.51 vs. 1.72 ± 0.78 × 10(-3)mmHg(-1), p = 0.380), descending thoracic aorta (2.69 ± 1.79 vs. 2.21 ± 0.79 × 10(-3)mmHg(-1), p = 0.181) nor in PWV (8.69 ± 6.76 vs. 10.23 ± 7.88 ms(-1), p = 0.301) at 6 m. CONCLUSIONS: Treatment of symptomatic severe aortic stenosis by SAVR but not TAVI was associated with an increase in aortic stiffness at 6 months. Future work should focus on the prognostic implication of these findings to determine whether improved patient selection and outcomes can be achieved.

Ventricular longitudinal function is associated with microvascular obstruction and intramyocardial haemorrhage.

BACKGROUND: Microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) are associated with adverse prognosis, independently of infarct size after reperfused ST-elevation myocardial infarction (STEMI). Mitral annular plane systolic excursion (MAPSE) is a well-established parameter of longitudinal function on echocardiography. OBJECTIVE: We aimed to investigate how acute MAPSE, assessed by a four-chamber cine-cardiovascular MR (CMR), is associated with MVO, IMH and convalescent left ventricular (LV) remodelling. METHODS: 54 consecutive patients underwent CMR at 3T (Intera CV, Philips Healthcare, Best, The Netherlands) within 3 days of reperfused STEMI. Cine, T2-weighted, T2* and late gadolinium enhancement (LGE) imaging were performed. Infarct and MVO extent were measured from LGE images. The presence of IMH was investigated by combined analysis of T2w and T2* images. Averaged-MAPSE (medial-MAPSE+lateral-MAPSE/2) was calculated from 4-chamber cine imaging. RESULTS: 44 patients completed the baseline scan and 38 patients completed 3-month scans. 26 (59%) patients had MVO and 25 (57%) patients had IMH. Presence of MVO and IMH were associated with lower averaged-MAPSE (11.7±0.4 mm vs 9.3±0.3 mm; p<0.001 and 11.8±0.4 mm vs 9.2±0.3 mm; p<0.001, respectively). IMH (ß=-0.655, p<0.001) and MVO (ß=-0.567, p<0.001) demonstrated a stronger correlation to MAPSE than other demographic and infarct characteristics. MAPSE ≤10.6 mm demonstrated 89% sensitivity and 72% specificity for the detection of MVO and 92% sensitivity and 74% specificity for IMH. LV remodelling in convalescence was not associated with MAPSE (AUC 0.62, 95% CI 0.44 to 0.77, p=0.22). CONCLUSIONS: Postreperfused STEMI, LV longitudinal function assessed by MAPSE can independently predict the presence of MVO and IMH.

Consequence of cerebral embolism after transcatheter aortic valve implantation compared with contemporary surgical aortic valve replacement: effect on health-related quality of life.

BACKGROUND: Incidence of cerebral microinfarcts is higher after transcatheter aortic valve implantation (TAVI) compared with surgical aortic valve replacement (SAVR). It is unknown whether these lesions persist and what direct impact they have on health-related quality of life. The objective was to identify predictors of cerebral microinfarction and measure their effect on health-related quality of life during 6 months after TAVI when compared with SAVR. METHODS AND RESULTS: Cerebral MRI was conducted at baseline, post procedure, and 6 months using diffusion-weighted imaging. Health-related quality of life was measured at baseline, 30 days, and 6 months with short form-12 health outcomes and EuroQol 5 dimensions questionnaires. One hundred eleven patients (TAVI, n=71; SAVR, n=40) were studied. The incidence (54 [77%] versus 17 [43%]; P=0.001) and number (3.4±4.9 versus 1.2±1.8; P=0.001) of new microinfarcts were greater after TAVI than after SAVR. The total volume per microinfarct was smaller in TAVI than in SAVR (0.23±0.24 versus 0.76±1.8 mL; P=0.04). The strongest associations for microinfarction were: TAVI (arch atheroma grade: r=0.46; P=0.0001) and SAVR (concomitant coronary artery bypass grafting: r=-0.33; P=0.03). Physical component score in TAVI increased after 30 days (32.1±6.6 versus 38.9±7.0; P<0.0001) and 6 months (40.4±9.3; P<0.0001); the improvement occurred later in SAVR (baseline: 34.9±10.6; 30 days: 35.9±10.2; 6 months: 42.8±11.2; P<0.001). After TAVI, there were no differences in the short form-12 health outcome scores according to the presence or size of new cerebral infarction. CONCLUSIONS: Cerebral microinfarctions are more common after TAVI compared with SAVR but seem to have no negative effect on early (30 days) or medium term (6 months) health-related quality of life. Aortic atheroma (TAVI) and concomitant coronary artery bypass grafting (SAVR) are independent risk factors for cerebral microinfarction.