Pellikka, Patricia A.

Background Carcinoid heart disease characteristically affects tricuspid (TV) and pulmonary valves (PV), and TV replacement is helpful in selected patients. There is uncertainty, however, regarding optimal surgical management of PV regurgitation. Methods and Results We reviewed 22 patients having operation for carcinoid heart disease and compared those having TV and PV replacement (n=12), to those who underwent TV replacement and excision of the PV (n=10). Pre- and postoperative right ventricular (RV) size and dysfunction were assessed by consensus of 2 echocardiographers blinded to type of surgical treatment. RV dysfunction was graded as none (0), mild (1), moderate (2), or severe (3). RV size was graded as normal (0), or mild (1), moderate (2), or severe (3) enlargement. Preoperatively, RV size (2.2±0.8 [no PVR]versus 2.7±0.6 [with PVR], P =0.15), RV dysfunction (0.9±0.9 [no PVR]versus 1.4±0.7 [with PVR], P =0.14), and NYHA class were similar in the 2 groups. Postop RV size decreased inpatients with PVR, 2.7±0.6 to 1.7±1.0 ( P =0.008), but did not change appreciably in those without PVR, 2.2±0.8 to 2.3±0.8 ( P =0.67). There was no significant change in RV dysfunction after surgery, 1.4±0.7 to 1.8±0.9 with PVR ( P =0.26) and 0.9±0.9 to 1.6±0.9 without PVR ( P =0.07). Conclusions PV replacement appears to have a beneficial effect on RV size in patients after surgery for carcinoid heart disease. This may have important implications for RV remodeling after PV replacement.

Introduction: Intrinsic wave propagation is a novel approach to measure myocardial stiffness (MS) as validated in animal studies. Aims and Hypothesis: 1) To compare MS measured by the wave method with chamber stiffness (CS) derived from noninvasively estimated end-diastolic pressure-volume relationship (EDPVR) in patients; 2) To test the hypothesis that MS is superior to CS for predicting outcomes in patients with cardiac amyloidosis (CA). Methods: Prospective study in 56 patients with amyloidosis (CA: 38, noncardiac amyloidosis, NCA: 18; 90% AL-type; age 63 ± 10 yrs; ejection fraction 57 ± 11%) and 36 normal subjects (age 49 ± 13 years). Intrinsic velocity propagation of myocardial stretch (iVP), a measure of MS, was measured by ultra-high frame rate (250-465Hz) tissue Doppler imaging. Left ventricular (LV) EDPVR were reconstructed using the noninvasive single-beat method (Fig.A). Stiffness coefficients (α, β, load-independent) and CS (dP/dV) were calculated. End-diastolic pressure (EDP) was estimated from E/e’. Adverse events at follow-up (death, heart failure, stroke, significant arrhythmia) were recorded. Results: iVP was higher in CA compared to NCA and controls, indicating higher MS (Fig. B). This was confirmed by EDPVR, which were steeper and shifted leftward (Fig. A). The slope (β) of EDPVR and CS (dP/dV) were higher and LV capacitance (V 30 , volume at 30 mmHg) was lower in CA (Fig. A) and correlated with iVP (β: r = 0.59; CS dP/dV, r = 0.43; EDP, r = 0.61; all p<0.0001). Patients with higher LV thickness (r = 0.66), lower LV longitudinal strain (r = -0.57) and elevated NT-proBNP (r = 0.69) had higher iVP. At follow-up (median 2.5 years), after adjusting for relevant confounders, an iVP >2.7 m/s was strongly associated with excess events (p<0.0001; Fig. C) and was superior to measures of CS (dP/dV: p = 0.28; β >6.5: p = 0.03; Fig. D). Conclusions: Myocardial stiffness by intrinsic wave method shows similar findings to chamber stiffness by EDVPR, but is more strongly related to outcomes in patients with amyloidosis.

Introduction: Bioprosthetic valve thrombosis (BPVT) is increasingly being recognized as a cause of prosthetic valve dysfunction within the first years after surgical implantation. However, in the absence of changes in clinical status, current guidelines recommend cardiac imaging only after 10 years post bioprosthetic valve implantation . Hypothesis: We hypothesized that an increase in prosthetic valve gradient is detectable months before a formal diagnosis of symptomatic BPVT. Methods: Eighty-three patients diagnosed with BPVT and treated medically at our institution between 2002 and 2017 were retrospectively identified. Transvalvular gradients recorded on TTE immediately post implantation, at time of clinical BPVT diagnosis, and within a 12-month period prior to BPVT diagnosis were available in 45 patients: 18 for the aortic position, 11 for mitral, and 16 for tricuspid. When more than one study was conducted in the 12 months’ timeframe, the latest value was used in the analysis. Data are reported as mean (95% CI). Results: For all valve positions, an increased gradient was detectable within 12 months prior to formal BPVT diagnosis: mean increase vs. baseline of 17 (10-23) mmHg, p < 0.0001 for aortic prostheses; 5 (2-8) mmHg, p = 0.004 for mitral prostheses, and 2 mm Hg (1-3) mmHg, p = 0.003 for tricuspid prostheses. The figure presents the evolution of prosthetic valve gradients (normalized to the baseline, immediately post-implantation value) in patients with aortic (left), mitral (middle), and tricuspid (right) valve . Conclusions: Elevated gradients precede formal clinical diagnosis of BPVT. Closer monitoring of transvalvular gradients may prove useful for BPVT diagnosis before patients become symptomatic. With recent evidence supporting the efficacy of anticoagulant therapy in BPVT, earlier diagnosis may lead to an increased rate of response and better clinical outcomes.

Background: Two-dimensional volumetric exercise stress echocardiography (ESE) provides an integrated view of left ventricular (LV) preload reserve through end-diastolic volume (EDV) and LV contractile reserve (LVCR) through end-systolic volume (ESV) changes. Purpose: To assess the dependence of cardiac reserve upon LVCR, EDV, and heart rate (HR) during ESE. Methods: We prospectively performed semi-supine bicycle or treadmill ESE in 1344 patients (age 59.8 ± 11.4 years; ejection fraction = 63 ± 8%) referred for known or suspected coronary artery disease. All patients had negative ESE by wall motion criteria. EDV and ESV were measured by biplane Simpson rule with 2-dimensional echocardiography. Cardiac index reserve was identified by peak-rest value. LVCR was the stress-rest ratio of force (systolic blood pressure by cuff sphygmomanometer/ESV, abnormal values ≤2.0). Preload reserve was defined by an increase in EDV. Cardiac index was calculated as stroke volume index * HR (by EKG). HR reserve (stress/rest ratio) <1.85 identified chronotropic incompetence. Results: Of the 1344 patients, 448 were in the lowest tertile of cardiac index reserve with stress. Of them, 303 (67.6%) achieved HR reserve <1.85; 252 (56.3%) had an abnormal LVCR and 341 (76.1%) a reduction of preload reserve, with 446 patients (99.6%) showing ≥1 abnormality. At binary logistic regression analysis, reduced preload reserve (odds ratio [OR]: 5.610; 95% confidence intervals [CI]: 4.025 to 7.821), chronotropic incompetence (OR: 3.923, 95% CI: 2.915 to 5.279), and abnormal LVCR (OR: 1.579; 95% CI: 1.105 to 2.259) were independently associated with lowest tertile of cardiac index reserve at peak stress. Conclusions: Heart rate assessment and volumetric echocardiography during ESE identify the heterogeneity of hemodynamic phenotypes of impaired chronotropic, preload or LVCR underlying a reduced cardiac reserve.

Background Aortic stenosis (AS) affects, and is associated with significant comorbidity and mortality, including sudden cardiac death (SCD) from unknown mechanisms. However, it is difficult to predict which patients with AS will suffer a SCD event. Anemia and low iron are known risk factors for mortality in heart failure populations and AS. We hypothesized that anemia in patients with AS is associated with increased risk of SCD. Purpose Understand the relationship and prognostic implications between anemia and SCD in patients with severe AS. Methods and Results We selected 8,144 of 10,850 patients with severe AS (mean transvalvular gradient ≥40 mmHg or peak velocity ≥4 m/s or calculated valve area < 1 cm 2 ) from the Mayo Clinic Aortic Stenosis Registry, which includes all consecutive patients with severe AS over the time period January 1 st , 1983 to September 30 th , 2015. Subjects in this analysis (median age 76 years and 57% male) were diagnosed starting in 1995 and had hemoglobin (Hb) measurements within one year of diagnosis and prior to intervention. The mean Hb level was 12.8 (± 1.9) g/dL. The prevalence of anemia (Hb<13.0g/dL for men, <12.0g/dL for women) was 40%, 14% microcytic, 20% macrocytic, with the remainder normocytic. Of the 8,144 patients, a total of 4,440 died (10‐year survival 39%; and 240 were confirmed as SCD events [10 year cumulative incidence 4%]). Anemia was associated with increased all‐cause mortality (HR 1.87, 95% CI 1.76–1.99, P=<0.001) and increased SCD events (HR 1.58, 95% CI 1.22–2.06, P=<0.001) in patients with severe AS. Every SD decrease in Hb (1.9 g/dL) was associated with an increased risk of SCD (HR 1.42, 95% CI 1.24–1.62, P<0.001). Conclusions Anemia is highly prevalent in patients with severe aortic stenosis and is independently associated with increased all‐cause mortality, and more specifically with increased SCD risk. Possible mechanisms include anemia aggrevating myocardial hypoxia, increasing propensity for arrhythmia and abnormal Bezold‐Jarisch reflex mismatch. Anemia may be a useful prognostic marker and a potential therapeutic target in patients with severe AS. Support or Funding Information CAAC is supported by AHA17POST33400211 and NIH HL134885. This study was supported by a grant from the Department of Cardiovascular Medicine, Mayo Clinic Rochester. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Background: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. Methods: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One Year in ISCHEMIA Trial Screen Failures With INOCA) was an international cohort study conducted from 2014 to 2019 involving angina assessments (Seattle Angina Questionnaire) and stress echocardiograms 1 year apart. This was an ancillary study that included patients with a history of angina who were not randomly assigned in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease status, and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between the changes in the Seattle Angina Questionnaire angina frequency score and changes in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and we compared CIAO participants with ISCHEMIA participants with obstructive coronary artery disease who had stress echocardiography before enrollment, as CIAO participants did. Results: INOCA participants in CIAO were more often female (66% of 208 versus 26% of 865 ISCHEMIA participants with obstructive coronary artery disease, P <0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [interquartile range, 3–5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO ( P =0.46) or ISCHEMIA stress echocardiography participants ( P =0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants, and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over 1 year was not significantly correlated with change in angina (ρ=0.029). Conclusions: Improvement in ischemia and angina were common in INOCA but not correlated. Our INOCA cohort had a degree of inducible wall motion abnormalities similar to concurrently enrolled ISCHEMIA participants with obstructive coronary artery disease. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02347215.

Objective Bioprosthetic valve thrombosis (BPVT) is increasingly recognised as a major cause of prosthetic dysfunction in the first years postimplantation. How early abnormal gradients can be detected prior to diagnosis and how fast they normalise with anticoagulant therapy is unknown. We set forth to (1) evaluate patterns of increase in gradients prior to BPVT diagnosis and (2) characterise time-course of response to anticoagulation. Methods Patients treated with warfarin for BPVT (1999–2019) with clinically significant reduction of mean gradients (≥25%) were identified retrospectively. Recovery was defined as gradient decrease ≥50%, to postimplantation or to normal-range gradients per position, model and size. Time-to-BPVT (implantation—BPVT diagnosis), potential diagnostic delay (first abnormal gradient by position, model and size—BPVT diagnosis) and time-to-recovery (BPVT diagnosis—complete resolution) were recorded. Results 77 patients were identified; 32 (42%) aortic (23 surgical—12 porcine, 11 pericardial; 9 transcatheter); 24 (31%) mitral; 21 (27%) tricuspid. Median time-to-BPVT was 24, 21 and 10 months, respectively. Potential diagnostic delay was median 21 months for aortic, 4 months for mitral, but 0 for tricuspid. Recovery was significantly faster in mitral than aortic (median 2.5 vs 4.8 months, p=0.038) and tricuspid (median 5.9 months, p=0.025) positions. Porcine aortic valves responded faster than pericardial aortic valves (median 2.9 vs 20.3 months, p=0.004). Conclusion Gradients start to increase months before the clinical BPVT diagnosis. Recovery is faster in mitral and surgical aortic porcine valves; a longer warfarin trial seems indicated in tricuspid and surgical aortic pericardial valves.

Background: Warfarin is known to be effective in the treatment of bioprosthetic valve thrombosis (BPVT). However, the time-course of response to anticoagulation has not been fully characterized. Hypothesis: We hypothesized that response to warfarin can differ depending on valve position. Methods: We retrospectively identified 45 patients with BPVT diagnosis between 2002 and 2019 that involved either the mitral (MV) or the aortic valve (AV) prostheses, all with eventual echocardiographic resolution with warfarin. BPVT involved AV in 26 (57.8%) patients and MV in 19 (42.2%). Mean gradients (MGs) were tracked starting from BPVT diagnosis until recovery, which was defined as MGs decreasing to initial post-implantation MGs, to 50% below MGs at BPVT diagnosis, or to < 20 mmHg in AV and < 5 mmHg in MV. Kaplan Meier analysis was used to compare recovery time between MV and AV. Duration is reported relative to the time of BPVT diagnosis. Results: Recovery was faster in MV than in AV patients treated with warfarin, with median time of 3.8 months in the AV and 1.8 months in the MV group, p < 0.001 (Figure 1). At 1 month follow up, 15.4% recovered in AV group and 21.1% in MV, p = 0.605. At 3 months, 38.5% recovered in the AV and 78.9% in the MV, p = 0.009. At 6 months, 57.7% of AV group recovered while 100% recovered in the MV group, p = 0.001. The longest time for recovery was 30 months in 1 AV patient. Conclusion: Recovery using warfarin tended to be faster in BPVT involving the MV compared with the AV. In our study, all patients with MV BPVT recovered by 6 months, while this only happened in half the patients with AV BPVT. This suggests that a longer duration of warfarin trial may be needed in the case of AV disease. This might also suggest that the pathogenesis may differ between the two valves.

Echocardiography (Echo), a widely available, noninvasive, and portable bedside imaging tool, is the most frequently used imaging modality in assessing cardiac anatomy and function in clinical practice. On the other hand, its operator dependability introduces variability in image acquisition, measurements, and interpretation. To reduce these variabilities, there is an increasing demand for an operator- and interpreter-independent Echo system empowered with artificial intelligence (AI), which has been incorporated into diverse areas of clinical medicine. Recent advances in AI applications in computer vision have enabled us to identify conceptual and complex imaging features with the self-learning ability of AI models and efficient parallel computing power. This has resulted in vast opportunities such as providing AI models that are robust to variations with generalizability for instantaneous image quality control, aiding in the acquisition of optimal images and diagnosis of complex diseases, and improving the clinical workflow of cardiac ultrasound. In this review, we provide a state-of-the art overview of AI-empowered Echo applications in cardiology and future trends for AI-powered Echo technology that standardize measurements, aid physicians in diagnosing cardiac diseases, optimize Echo workflow in clinics, and ultimately, reduce healthcare costs.

Abstract Aims Beat-to-beat variability in cycle length is well-known in atrial fibrillation (Afib); whether this also translates to variability in annulus size remains unknown. Defining annulus maximal size in Afib is critical for accurate selection of percutaneous devices given the frequent association with mitral and tricuspid valve diseases. Methods and results Images were obtained from 170 patients undergoing 3D echocardiography [100 (50 sinus rhythm (SR) and 50 Afib) for mitral annulus (MA) and 70 (35 SR and 35 Afib) for tricuspid annulus (TA)]. Images were analysed for differences in annular dynamics with a commercially available software. Number of cardiac cycles analysed was 567 in mitral valve and 346 in tricuspid valve. Median absolute difference in maximal MA area over four to six cycles was 1.8 cm2 (range 0.5–5.2 cm2) in Afib vs. 0.8 cm2 (range 0.1–2.9 cm2) in SR, P &lt; 0.001. Maximal MA area was observed within 30–70% of the R-R interval in 81% of cardiac cycles in SR and in 73% of cycles in Afib. Median absolute difference in maximal TA area over four to six cycles was 1.4 cm2 (range 0.5–3.6 cm2) in Afib vs. 0.7 cm2 (range 0.3–1.7 cm2) in SR, P &lt; 0.001. Maximal TA area was observed within 60–100% of the R-R interval in 81% of cardiac cycles in SR, but only in 49% of cycles in Afib. Conclusion MA and TA reach maximal size within a broad time interval centred around end-systole and end-diastole, respectively, with significant beat-to-beat variability. Afib leads to a larger beat-to-beat variability in both timing of occurrence and values of annulus size than in SR.