Pislaru, Sorin V.

Abstract Background: Aortic stenosis (AS) causes left ventricular (LV) pressure overload, leading to adverse LV remodeling and dysfunction. We examined the impact of severe AS and its consequent increase in LV afterload on myocardial deformation and rotational mechanics by 2-dimensional (2D) and 3-dimensional (3D) speckle-tracking echocardiography. Methods: We prospectively measured various strain parameters in 168 patients (42% female, mean age 72±12 years) with severe AS and LV ejection fraction (EF) ≥50%, and compared them to normal values found in literature. 2D and 3D images were analyzed for global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), basal rotation, apical rotation, and peak systolic twist. We further assessed the degree of concordance between 2D and 3D strain, and examined their association with measures of LV preload and afterload. Results: Patients with severe AS exhibited significantly lower GLS and GRS but higher GCS, apical rotation, and twist by 2D and 3D echocardiography compared with published normal values (P=0.003 for 3D twist,P<0.001 for all others). There was modest agreement between 2D and 3D GLS measurements (concordance correlation coefficient 0.49, 95% confidence interval 0.39-0.57). GLS was modestly correlated with valvulo-arterial impedance, a measure of LV afterload (r=0.34, p<0.001 for 2D and r=0.23, p=0.003 for 3D). Conclusion: Patients with severe AS demonstrate lower-than-normal GLS and GRS as a result of increased afterload but appear to compensate with higher-than-normal GCS, apical rotation, and twist in order to maintain a preserved LVEF. Our study provides, to our knowledge, the most comprehensive analysis to date of myocardial deformation and rotational mechanics by 2D and 3D speckle-tracking echocardiography in patients with severe AS and preserved LVEF.

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 &gt;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 &lt; 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 Secondary mitral regurgitation (SMR) impacts outcomes in heart failure with reduced ejection fraction (HFrEF) but whether it is a specific therapeutic target in heart failure patients with preserved ejection fraction (HFpEF) is less clear. Purpose The aims of this study were to investigate whether surgical or trans-catheter intervention reduces SMR and improves outcomes compared to optimal medical therapy in HFpEF patients. Methods We retrospectively identified 120 HFpEF patients with moderate-to-severe or greater SMR from January 1, 2007, until December 31, 2017. Moderate-to-severe SMR was defined as an effective regurgitant orifice area of >0.3cm2, and/or a regurgitation volume of >45ml per beat. Those with primary mitral regurgitation, endocarditis, HFrEF, hypertrophic cardiomyopathy, congenital heart disease, and history of valve intervention were excluded. All-cause mortality was analyzed and correlated to clinical and echocardiographic characteristics. Amongst the 120 patients, 36 received surgical or trans-catheter procedure in addition to medical therapy (procedure group) and 84 patients received optimal medical therapy only (conservative treatment group). The median follow-up period was 864 (15–3553) days. Results Patients in the procedure group were younger (75±8 vs 81±10, P=0.0002) and with fewer comorbidities (Charlson Comorbidity Index 7.0±2.4 vs 8.0±2.0, P=0.022) compared to the conservative treatment group. In addition, the procedure group had larger left ventricular end-diastolic diameters and higher SMR volume at baseline. During follow-up, SMR decreased by ≥2 grades in 75% of patients (27/36) in the procedure group compared to 20% of patients (12/60) in the conservative treatment group. After adjusting for age and comorbidities, the procedure group showed better overall survival compared to the conservative treatment group (HR 0.37; 95% CI 0.17–0.80; P=0.011). On multivariate analysis for the different groups (procedure group vs. conservative treatment group) (HR 0.40; 95% CI 0.17–0.91; P=0.019), increasing Charlson Comorbidity Index (HR 1.16; 95% CI 1.02–1.32; P=0.028) and average mitral E/e' ratio (HR 1.06; 95% CI 1.01–1.11; P=0.031) were independent predictors of increased all-cause mortality. Kaplan-Meier Survival Curve Conclusion Among heart failure patients with preserved ejection fraction and moderate-to-severe or severe SMR, surgical or trans-catheter mitral-valve repair or replacement resulted in lower all-cause mortality compared to conservative treatment after 9 years of follow-up.

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.

Abstract Background Left ventricular ejection fraction (LVEF), end diastolic, end systolic volumes (EDV, ESV) and global longitudinal strain (GLS) are very important parameters that are frequently reported in cardiology. Normal cardiac geometry was not considered in articles that published normal values. It is important to know normal parameters for population studies. Our hypothesis is to analyze how EF, volumes and GLS may vary by age groups, gender and BMI in a population with normal cardiac geometry. Purpose To define the values in EF, volumes and GLS measurements in a healthy population with normal cardiac geometry stratified by age groups, gender and body mass index (BMI). Methods This is a single center retrospective study conducted from 2008 to 2018. We selected 4557 subjects (2605 females, 1952 males) >18 years with ≤ mild valvular heart disease, who underwent 2D-echocardiography (2DE) at Mayo clinic, Rochester. All selected subjects had normal LV geometry (i.e., LV mass index≤88g/m2 in females and ≤102g/m2 in males and relative wall thickness ≤0.42 measured by 2DE) and without any cardiovascular risk factors or structural or functional abnormality determined by 2DE. Based on age groups, gender and BMI, we assessed the variability in volumes indexed to body surface area, EF and GLS by Mean ± SD and two sample t-test. Results Mean age was 54±15 years (females = 53±15, males = 56±16), body surface area was 1.9 m2±0.2 (females = 1.8±0.2, males = 2.1±0.2), LV GLS −20.7% ±2 SD (females = −21.2±2, males= −20.2±1.9) ranging −16.1 to −27.6 in both genders (Figure); LVEF by Biplane volume method 62.6% ± 4 SD (females = 63±4.3, males=62±4.5). The end diastolic volume 63.6±11.7 cc/m2 (female = 59.9±10.3, males = 68.1±11.8) and end systolic volume 23.9 cc/m2±5.4 (female = 22.3±4.8, males = 25.9±5.5). LV GLS, Biplane EF values were higher in females and EDV and ESV values were higher in males. LV GLS values decreased with age in females (P<0.0001). While EF increased with age in both genders (P<0.0001), EDV and ESV values decreased with age (P<0.0001). When each gender is sub-divided based on their BMI (<25 and ≥25), GLS, EDV and ESV values were higher in population with BMI <25 (P<0.0001). Normal geometry variables Conclusion To our knowledge, this is the biggest single center study to evaluate LV GLS values, LV EF, ED, ES volumes. These results can be used as reference values in a normal population. Acknowledgement/Funding None

Abstract Background Mild to moderate mitral regurgitation (MR) is a common finding in heart failure with preserved ejection fraction (HFpEF). MR is often considered to be an innocent bystander, yet little data is available regarding its implications. Aim Determine the pathophysiologic correlates of MR in HFpEF Methods We retrospectively studied 280 patients with invasively proven HFpEF. MR was absent (None or trivial) in 163 subjects (Non-MR-HFpEF), and present in 117 (MR-HFpEF; 78 mild and 39 moderate MR). 247 subjects also underwent invasive cardiopulmonary exercise testing. Results At rest, MR-HFpEF subjects displayed higher pulmonary artery pressures (PAP), PCWP, and pulmonary vascular resistance (PVR; Table). During exercise, PAP and PCWP were not significantly different among groups, but MR-HFpEF displayed reduced ability to enhance cardiac output (CO) in response to heightened metabolic demand (oxygen consumption, VO2; Figure). Baseline characteristics and haemodynamic characterization at baseline and peak exercise Baseline characteristics Non-MR-HFpEF (N=163) MR-HFpEF (N=117) p value Age 66±11 71±10 0.0002 Female (%) 56 69 0.02 AFib (%) 13 38 <0.0001 Nt proBNP 192 [66, 557] 870 [401, 2135] <0.0001 E/E' 12.3±5.5 15.6±7.2 0.0006 LVEF (%) 64±6 62±6 0.0001 RV fractional area change (%) 51±9 47±10 0.0001 Mean PA (mmHg) 25±7 28±9 0.001 Mean PCWP (mmHg) 15±5 17±6 0.0002 PVR (Woods) 2.0±1.1 2.5±1.4 0.015 CO (L/min) 5.5±1.6 4.8±1.3 0.12 Peak exercise hemodynamics Non-MR-HFpEF (N=152) MR-HFpEF (N=95) p value Mean PA (mmHg 45±10 46.5±10 0.07 Mean PCWP (mmHg) 32±6 31±6 0.6 PVR (Woods) 1.8±1.6 2.7±2.4 0.002 CO (L/min) 9.1±3 7.2±3 0.01 P value adjusted for age, gender and BMI. CO change in response to VO2 increase Conclusion The presence of even mild MR in HFpEF is associated with more adverse hemodynamics, greater pulmonary vascular dysfunction and impaired CO reserve with exercise. Further study is required to better understand the natural history and treatment for MR in HFpEF. Acknowledgement/Funding None

Background: The role of coronary microvascular disease and its impact on functional and energetic reserve in heart failure with preserved ejection fraction (HFpEF) remains unclear. We hypothesized that in response to submaximal pharmacologic stress (dobutamine), patients with HFpEF have impairment in left ventricular (LV) myocardial mechanical (external work [EW]), energetic (myocardial O 2 consumption [MVO 2 ]), and myocardial blood flow (MBF) reserve. We further assessed whether coupling of MBF to EW is impaired in HFpEF and associated with compensatory increases or pathological decreases in myocardial O 2 extraction. Lastly, we assessed whether coupling of MVO 2 to EW (mechanical efficiency) was impaired in HFpEF. Methods and Results: In prospectively enrolled patients with HFpEF (n=19) and age/sex-matched healthy controls (n=19), we performed 11 C-acetate positron emission tomography assessing MVO 2 and MBF at rest and during dobutamine infusion. EW was calculated as stroke volume (echo)×end-systolic pressure×heart rate. At rest, compared with controls, patients with HFpEF had higher LV EW, MVO 2 , and MBF. With dobutamine, LV EW, MVO 2 , and MBF increased in both HFpEF and controls; however, the magnitude of increases was significantly smaller in HFpEF. In both groups, MBF increased in relation to EW, but in HFpEF, the slope of the relationship was significantly smaller than in controls. Myocardial O 2 extraction was increased in HFpEF. Mechanical efficiency was similar in HFpEF and controls. In a post hoc analysis, HFpEF patients with LV hypertrophy (n=10) had significant reductions in LV mechanical efficiency relative to controls. Conclusions: In HFpEF during submaximal dobutamine stress, there is myocardial mechanical-, energetic- and flow-reserve dysfunction with impaired coupling of blood flow to demand and slight increases in myocardial O 2 extraction. These findings provide evidence that coronary microvascular dysfunction is present in HFpEF, limits O 2 supply relative to demand, and is associated with reserve dysfunction.

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 Background Pneumopericardium is an uncommon clinical finding. It most commonly occurs after chest trauma but can also emerge as a complication following interventional or surgical procedures and can result in life-threatening complications. A high index of clinical suspicion should be present and once the condition is recognized, it should be managed promptly. Paucity of literature on pneumopericardium makes outlining any new case of paramount importance to emphasize the aspects of diagnosis and management of this rare condition. Case summary A 59-year-old woman with severe mitral valve and moderate tricuspid valve regurgitation underwent mitral and tricuspid valve repair with uneventful post-operative in-hospital stay. She presented 10 days after discharge with progressive shortness of breath. Chest X-ray revealed right hydropneumothorax. Transthoracic echocardiography (TTE) performed in the emergency department showed an apparently small pericardial effusion with patient in supine position; the effusion size increased substantially when imaging in left lateral decubitus, with presence of intrapericardial air bubbles. Computed tomography scan of the chest confirmed the presence of right hydropneumothorax and hydropneumopericardium, with a communicating pleuro-pericardial tract. The patient underwent chest tube placement which successfully decompressed both pleural and pericardial space. Discussion Hydropneumopericardium is a rare post-operative complication. Comprehensive TTE with imaging from multiple acoustic windows is mandatory when evaluating the extent of pericardial effusion. Presence of cardiac tamponade is crucial in determining the management plan.