Pislaru, Cristina

Abstract Aims Cardiac power is a measure of cardiac performance that incorporates both pressure and flow components. Prior studies have shown that cardiac power predicts outcomes in patients with reduced left ventricular (LV) ejection fraction (EF). We sought to evaluate the prognostic significance of peak exercise cardiac power and power reserve in patients with normal EF. Methods and results We performed a retrospective analysis in 24 885 patients (age 59 ± 13 years, 45% females) with EF ≥50% and no significant valve disease or right ventricular dysfunction, undergoing exercise stress echocardiography between 2004 and 2018. Cardiac power and power reserve (developed power with stress) were normalized to LV mass and expressed in W/100 g of LV myocardium. Endpoints at follow-up were all-cause mortality and diagnosis of heart failure (HF). Patients in the higher quartiles of power/mass (rest, peak stress, and power reserve) were younger and had higher peak blood pressure and heart rate, lower LV mass, and lower prevalence of comorbidities. During follow-up [median 3.9 (0.6–8.3) years], 929 patients died. After adjusting for age, sex, metabolic equivalents (METs) achieved, ischaemia/infarction on stress test results, medication, and comorbidities, peak stress power/mass was independently associated with mortality [adjusted hazard ratio (HR), highest vs. lowest quartile, 0.5, 95% confidence interval (CI) 0.4–0.6, P < 0.001] and HF at follow-up [adjusted HR, highest vs. lowest quartile, 0.4, 95% CI (0.3, 0.5), P < 0.001]. Power reserve showed similar results. Conclusion The assessment of cardiac power during exercise stress echocardiography in patients with normal EF provides valuable prognostic information, in addition to stress test findings on inducible myocardial ischaemia and exercise capacity.

Abstract Aims Chronic volume-overload can impair systolic and diastolic myocardial properties. We tested the hypothesis that Intrinsic Cardiac Elastography may detect alterations in passive myocardial elasticity in patients with chronic severe mitral regurgitation (MR) and predict worsening left ventricular (LV) function after mitral valve repair (MVr). Methods and results Comprehensive transthoracic echocardiography and cardiac elastography were performed in 80 patients with primary MR (prolapse and/or flail leaflets) of varying severity and compared with 40 normal subjects. In patients who underwent MVr (n = 51), elastography measurements were related to changes in left ventricular ejection fraction (LVEF) at short-term (3–4 days post-op) and mid-term (1 year) follow-up. Most patients were asymptomatic or mildly symptomatic and had preserved LVEF (>60%). Intrinsic velocity propagation (iVP) of myocardial stretch, a direct measure of myocardial stiffness, was higher in patients with severe MR {median 2.0 [interquartile range (IQR) 1.5–2.2] m/s, range 1.1–3.4 m/s; n = 56} compared to normal subjects [median 1.7 (IQR 1.5–1.8) m/s; n = 40; P = 0.0005], but not in those with mild or moderate MR [median 1.7 (IQR 1.4–1.9) m/s; n = 24]. A higher iVP was associated with more severe LV volume-overload and LV and left atrial enlargement (P < 0.05 for all). In patients undergoing MVr, a higher iVP independently predicted a larger drop in LVEF post-intervention (short-term, P = 0.001; 1 year, P = 0.007), incrementally to pre-operative LVEF (P < 0.05). Conclusion Non-invasive measurements of myocardial stiffness were able to predict functional deterioration after MVr for chronic primary MR. Further studies should investigate the mechanisms and practical utility of this novel measurement.

Abstract Aims Despite improvements in cardiac haemodynamics and symptoms, long-term mortality remains increased in some patients after aortic valve replacement (AVR). Limited data exist on the prognostic role of left ventricular (LV) chamber stiffening in these patients. Methods and results We performed a retrospective analysis in 1893 patients with severe aortic stenosis (AS) referred for AVR. LV end-diastolic pressure–volume relations (EDPVR, P = αV^β) were reconstructed from echocardiographic measurements of end-diastolic volumes and estimates of end-diastolic pressure (EDP). The impact of EDPVR-derived LV chamber stiffness (CS30, at 30 mmHg EDP) on all-cause mortality after AVR was evaluated. Mean age was 76 ± 10 years, 39% were females, and ejection fraction (EF) was 61 ± 12%. The mean LV chamber stiffness (CS30) was 2.2 ± 1.3 mmHg/mL. A total of 877 (46%) patients had high LV stiffness (CS30 >2 mmHg/mL). In these patients, the EDPVR curves were steeper and shifted leftwards, indicating higher stiffness at all pressure levels. These patients were slightly older, more often female, and had more prevalent comorbidities compared to patients with low stiffness. At follow-up [median 4.2 (interquartile range 2.8–6.3) years; 675 deaths], a higher CS30 was associated with lower survival (hazard ratio: 2.7 for severe vs. mild LV stiffening; P < 0.0001), both in patients with normal or reduced EF. At multivariate analysis, CS30 remained an independent predictor, even after adjusting for age, sex, comorbidities, EF, LV remodelling, and diastolic dysfunction. Conclusion Higher preoperative LV chamber stiffening in patients with severe AS is associated with poorer outcome despite successful AVR.

Abstract Background Cardiac power output-to-mass (CPOM) ratio is a measure of myocardial performance that incorporates both pressure and flow output, normalized to left ventricular (LV) mass generating that cardiac work. Prior small studies have shown that CPOM predicts outcomes in patients with ischemic cardiomyopathy and reduced LV ejection fraction (EF). We sought to evaluate the prognostic significance of peak exercise CPOM and power reserve (increase from rest to peak exercise) in patients with normal EF. Methods and results Retrospective study in 24,783 patients (age 59±13 years, 45% females) with EF≥50% and no significant valve disease or right ventricular (RV) dysfunction, undergoing exercise stress echocardiography between 2004–2018. CPOM was calculated as previously described (0.222 x cardiac output x mean blood pressure / LV mass) and expressed in Watts/100g myocardium. Power reserve was calculated as difference in CPOM between peak stress and rest. All-cause mortality was the primary endpoint. Patients were divided into quartiles of power reserve. Patients with higher power reserve were younger, had higher blood pressure and heart rate, lower LV mass, and lower prevalence of prior myocardial infarction. (Table). During follow-up (median (IQR) 3.9 (0.6–8.3) years), 931 (3.8%) patients died. Progressively lower power reserve was associated with increasing mortality (Figure A). Compared to patients with abnormal stress test, patients with the lowest power reserve but otherwise normal stress test had the same survival as those with infarction/cardiomyopathy or ischemia on stress test (Figure B). Resting CPOM had lower predictive value. After adjusting for age, sex, METs achieved, ischemia/infarction on stress test results, and diastolic function grade, both peak exercise CPOM and power reserve were independent predictors of mortality (p<0.0001), incremental to conventional measures. Conclusion Cardiac power output and reserve measured during exercise stress echo provides independent prognostic information in patients with normal resting EF and no significant valve disease or RV dysfunction. The survival of patients with low power reserve but normal stress test was similar to patients with prior infarction/ cardiomyopathy or ischemia on stress test.

Background: Mitral stenosis frequently coexists in patients with severe aortic stenosis. Mitral stenosis severity evaluation is challenging in the setting of combined aortic stenosis and mitral stenosis because of hemodynamic interactions between the 2 valve lesions. The impact of aortic valve replacement (AVR) for severe aortic stenosis on mitral stenosis is unknown. This study aimed to assess the effect of AVR on mitral stenosis hemodynamics and the clinical outcomes of patients with severe aortic stenosis with and without mitral stenosis. Methods: We retrospectively investigated patients who underwent surgical AVR or transcatheter AVR for severe aortic stenosis from 2008 to 2015. Mean transmitral gradient by Doppler echocardiography ≥4 mm Hg was identified as mitral stenosis; patients were then stratified according to mitral valve area (MVA, by continuity equation) as >2.0 cm 2 or ≤2.0 cm 2 . MVA before and after AVR in patients with mitral stenosis were evaluated. Clinical outcomes of patients with and without mitral stenosis were compared using 1:2 matching for age, sex, left ventricular ejection fraction, method of AVR (surgical AVR versus transcatheter AVR) and year of AVR. Results: Of 190 patients with severe aortic stenosis and mitral stenosis (age 76±9 years, 42% men), 184 were matched with 362 with severe aortic stenosis without mitral stenosis. Among all mitral stenosis patients, the mean MVA increased after AVR by 0.26±0.59 cm 2 (from 2.00±0.50 to 2.26±0.62 cm 2 , P <0.01). MVA increased in 105 (55%) and remained unchanged in 34 (18%). Indexed stroke volume ≤45 mL/m 2 (odds ratio [OR] 2.40; 95% CI, 1.15–5.01; P =0.020) and transcatheter AVR (OR, 2.36; 95% CI, 1.17–4.77; P =0.017) were independently associated with increase in MVA. Of 107 with significant mitral stenosis (MVA ≤2.0 cm 2 ), MVA increased to >2.0 cm 2 after AVR in 52 (49%, pseudo mitral stenosis) and remained ≤2.0 cm 2 in 55 (51%, true mitral stenosis). During follow-up of median 2.9 (0.7–4.9) years, true mitral stenosis was an independent predictor of all-cause mortality (adjusted hazard ratio, 1.88; 95% CI, 1.20–2.94; P <0.01). Conclusions: MVA improved after AVR in nearly half of patients with severe aortic stenosis and mitral stenosis. MVA remained ≤2.0 cm 2 (true mitral stenosis) in nearly half of patients with severe aortic stenosis and significant mitral stenosis; this was associated with worse survival among patients undergoing AVR for severe aortic stenosis.

Abstract Diastolic dysfunction causes close to half of congestive heart failures and is associated with increased stiffness in left-ventricular myocardium. A clinical tool capable of measuring viscoelasticity of the myocardium could be beneficial in clinical settings. We used Lamb wave Dispersion Ultrasound Vibrometry (LDUV) for assessing the feasibility of making in vivo non-invasive measurements of myocardial elasticity and viscosity in pigs. In vivo open-chest measurements of myocardial elasticity and viscosity obtained using a Fourier space based analysis of Lamb wave dispersion are reported. The approach was used to perform ECG-gated transthoracic in vivo measurements of group velocity, elasticity and viscosity throughout a single heart cycle. Group velocity, elasticity and viscosity in the frequency range 50–500 Hz increased from diastole to systole, consistent with contraction and relaxation of the myocardium. Systolic group velocity, elasticity and viscosity were 5.0 m s −1 , 19.1 kPa, 6.8 Pa · s, respectively. In diastole, the measured group velocity, elasticity and viscosity were 1.5 m s −1 , 5.1 kPa and 3.2 Pa · s, respectively.

We have proposed generating a bending wave in the arterial wall using ultrasound radiation force and measuring the wave velocity along the arterial wall [Zhang et al., IEEE Trans. Ultrason. Ferroelectr. Freq. Control 52, 642–652 (2005)]. Here, we report the results of in vivo studies on pigs. The pig was anesthetized, and a micromanometer tip catheter was inserted into the femoral artery to measure luminal pressure. A water bath was created on the animal’s groin to allow unimpeded access of the ultrasound beams to the femoral artery. The femoral artery was first located using a 13-MHz linear-array transducer. Then, a vibro-acoustography image was obtained to ensure precise positioning of the excitation force relative to the artery. The artery was excited by the force transducer and the resulting vibration of the arterial wall was measured by a sensing Doppler transceiver. Measured wave velocity was 3.1 m/s at 300 Hz. With this new method wave velocity over a distance of 5 mm, and therefore stiffness of arteries, can be measured locally and non-invasively. Measurement time is short in a few tens of milliseconds, which allows pressure dependence and pharmacological effect on the wall properties to be measured at different cardiac times.