Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Cardiac Magnetic Resonance Study

ObjectivesThis study examined fibrosis progression in hypertrophic cardiomyopathy (HCM) patients, as well as its relationship to patient characteristics, clinical outcomes, and its effect on clinical decision making.BackgroundMyocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information in patients with HCM.MethodsA total of 157 patients with HCM were enrolled in this study, with 2 sequential CMR scans separated by an interval of 4.7 ± 1.9 years.ResultsAt the first CMR session (CMR-1), 70% of patients had LGE compared with 85% at CMR-2 (p = 0.001). The extent of LGE extent increased between the 2 CMR procedures, from 4.0 ± 5.6% to 6.3 ± 7.4% (p < 0.0001), with an average LGE progression rate of 0.5 ± 1.0%/year. LGE mass progression was correlated with higher LGE mass and extent on CMR-1 (p = 0.0017 and p = 0.007, respectively), greater indexed left ventricular (LV) mass (p < 0.0001), greater LV maximal wall thickness (p < 0.0001), apical aneurysm at CMR-1 (p < 0.0001), and lower LV ejection fraction (EF) (p = 0.029). Patients who were more likely to have a higher rate of LGE progression presented with more severe disease at baseline, characterized by LGE extent >8% of LV mass, indexed LV mass >100 g/m², maximal wall thickness ≥20 mm, LVEF ≤60%, and apical aneurysm. There was a significant correlation between the magnitude of LGE progression and future implantation of insertable cardioverter-defibrillators (p = 0.004), EF deterioration to ≤50% (p < 0.0001), and admission for heart failure (p = 0.0006).ConclusionsMyocardial fibrosis in patients with HCM is a slowly progressive process. Progression of LGE is significantly correlated with a number of clinical outcomes such as progression to EF ≤50% and heart failure admission. Judicious use of serial CMR with LGE can provide valuable information to help patient management.     

Effect of Ticagrelor on Left Ventricular Remodeling in Patients With ST-Segment Elevation Myocardial Infarction (HEALING-AMI)

ObjectivesThe aim of this study was to evaluate the effect of ticagrelor versus clopidogrel on left ventricular (LV) remodeling after reperfusion of ST-segment elevation myocardial infarction (STEMI) in humans.BackgroundAnimal studies have demonstrated that ticagrelor compared with clopidogrel better protects myocardium against reperfusion injury and improves remodeling after myocardial infarction.MethodsIn this investigator-initiated, randomized, open-label, assessor-blinded trial performed at 10 centers in Korea, patients were enrolled if they had naive STEMI successfully treated with primary percutaneous coronary intervention (PCI) and at least 6-month planned duration of dual-antiplatelet treatment. The coprimary endpoints were LV remodeling index (LVRI) (a relative change of LV end-diastolic volume) measured on 3-dimensional echocardiography and N-terminal pro–B-type natriuretic peptide level at 6 months.ResultsAmong initially enrolled patients with STEMI (n = 336), 139 in each group completed the study. LVRI at 6 months was numerically lower with ticagrelor versus clopidogrel (0.6 ± 18.6% vs. 4.5 ± 16.5%; p = 0.095). Ticagrelor significantly reduced the 6-month level of N-terminal pro–B-type natriuretic peptide (173 ± 141 pg/ml vs. 289 ± 585 pg/ml; p = 0.028). These differences were prominent in patients with pre-PCI TIMI (Thrombolysis In Myocardial Infarction) flow grade 0. By multivariate analysis, ticagrelor versus clopidogrel reduced the risk for positive LV remodeling (LVRI >0%) (odds ratio: 0.56; 95% confidence interval: 0.33 to 0.95; p = 0.030). The LV end-diastolic volume index remained unchanged during ticagrelor treatment (from 54.7 ± 12.2 to 54.2 ± 12.2 ml/m²; p = 0.629), but this value increased over time during clopidogrel treatment (from 54.6 ± 11.3 to 56.4 ± 13.9 ml/m²; p = 0.056) (difference −2.3 ml/m²; 95% confidence interval: −4.8 to 0.2 ml/m²; p = 0.073). Ticagrelor reduced LV end-systolic volume index (from 27.0 ± 8.5 to 24.7 ± 8.4 ml/m²; p < 0.001), whereas no reduction was seen with clopidogrel (from 26.2 ± 8.9 to 25.6 ± 11.0 ml/m²; p = 0.366) (difference −1.8 ml/m²; 95% confidence interval: −3.5 to −0.1 ml/m²; p = 0.040).ConclusionsTicagrelor was superior to clopidogrel for LV remodeling after reperfusion of STEMI with primary PCI. (High Platelet Inhibition With Ticagrelor to Improve Left Ventricular Remodeling in Patients With ST Segment Elevation Myocardial Infarction [HEALING-AMI]; NCT02224534)     

Empagliflozin Reduces Myocardial Extracellular Volume in Patients With Type 2 Diabetes and Coronary Artery Disease

ObjectivesThis study sought to evaluate the effects of empagliflozin on extracellular volume (ECV) in individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD).BackgroundEmpagliflozin has been shown to reduce left ventricular mass index (LVMi) in patients with T2DM and CAD. The effects on myocardial ECV are unknown.MethodsThis was a prespecified substudy of the EMPA-HEART (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes) CardioLink-6 trial in which 97 participants were randomized to receive empagliflozin 10 mg daily or placebo for 6 months. Data from 74 participants were included: 39 from the empagliflozin group and 35 from the placebo group. The main outcome was change in left ventricular ECV from baseline to 6 months determined by cardiac magnetic resonance (CMR). Other outcomes included change in LVMi, indexed intracellular compartment volume (iICV) and indexed extracellular compartment volume (iECV), and the fibrosis biomarkers soluble suppressor of tumorgenicity (sST2) and matrix metalloproteinase (MMP)-2.ResultsBaseline ECV was elevated in the empagliflozin group (29.6 ± 4.6%) and placebo group (30.6 ± 4.8%). Six months of empagliflozin therapy reduced ECV compared with placebo (adjusted difference: –1.40%; 95% confidence interval [CI]: –2.60 to –0.14%; p = 0.03). Empagliflozin therapy reduced iECV (adjusted difference: –1.5 ml/m²; 95% CI: –2.6 to –0.5 ml/m²; p = 0.006), with a trend toward reduction in iICV (adjusted difference: –1.7 ml/m²; 95% CI: –3.8 to 0.3 ml/m²; p = 0.09). Empagliflozin had no impact on MMP-2 or sST2.ConclusionsIn individuals with T2DM and CAD, 6 months of empagliflozin reduced ECV, iECV, and LVMi. No changes in MMP-2 and sST2 were seen. Further investigation into the mechanisms by which empagliflozin causes reverse remodeling is required. (Effects of Empagliflozin on Cardiac Structure in Patients With Type 2 Diabetes [EMPA-HEART]; NCT02998970)     

Hyperventilation/Breath-Hold Maneuver to Detect Myocardial Ischemia by Strain-Encoded CMR: Diagnostic Accuracy of a Needle-Free Stress Protocol

ObjectivesThe purpose of this study was to evaluate the diagnostic accuracy of a fast, needle-free test for myocardial ischemia using fast Strain-ENCoded (fSENC) cardiovascular MR (CMR) after a hyperventilation/breath-hold maneuver (HVBH).BackgroundMyocardial stress testing is one of the most frequent diagnostic tests performed. Recent data indicate that CMR first-pass perfusion outperforms other modalities. Its use, however, is limited by the need for both, a vasodilatory stress and the intravenous application of gadolinium. Both are associated with added cost, safety concerns, and patient inconvenience. The combination of 2 novel CMR approaches, fSENC, an ultrafast technique to visualize myocardial strain, and HVBH, a physiological vasodilator, may overcome these limitations.MethodsPatients referred for CMR stress testing underwent an extended protocol to evaluate 3 different tests: 1) adenosine-perfusion; 2) adenosine-strain; and 3) HVBH-strain. Diagnostic accuracy was assessed using quantitative coronary angiography as reference.ResultsA total of 122 patients (age 66 ± 11years; 80% men) suspected of obstructive coronary artery disease were enrolled. All participants completed the protocol without significant adverse events. Adenosine-strain and HVBH-strain provided significantly better diagnostic accuracy than adenosine-perfusion, both on a patient level (adenosine-strain: sensitivity 82%, specificity 83%; HVBH-strain: sensitivity 81%, specificity 86% vs. adenosine-perfusion: sensitivity 67%, specificity 92%; p < 0.05) and territory level (adenosine-strain: sensitivity 67%, specificity 93%; HVBH-strain: sensitivity 63%, specificity 95% vs. adenosine-perfusion: sensitivity 49%, specificity 96%; p < 0.05). However, these differences in diagnostic accuracy disappear by excluding patients with history of coronary artery bypass graft or previous myocardial infarction. The response of longitudinal strain differs significantly between ischemic and nonischemic segments to adenosine (ΔLS_ischemic = 0.6 ± 5.4%, ΔLS_nonischemic = −0.9 ± 2.7%; p < 0.05) and HVBH (ΔLS_ischemic = 1.3% ± 3.8%, ΔLS_nonischemic = −0.3 ± 1.8%; p = 0.002). Test duration of HVBH-strain (t = 64 ± 2 s) was significantly shorter compared with adenosine-strain (t = 184 ± 59 s; p < 0.0001) and adenosine-perfusion (t = adenosine-perfusion: 172 ± 59 s; p < 0.0001).ConclusionsHVBH-strain has a high diagnostic accuracy in detecting significant coronary artery stenosis. It is not only significantly faster than any other method but also neither requires contrast agents nor pharmacological stressors.     

Multiparametric Cardiac Magnetic Resonance Imaging Can Detect Acute Cardiac Allograft Rejection After Heart Transplantation

ObjectivesThe purpose of this study was to evaluate the sensitivity of multiparametric cardiac magnetic resonance imaging (CMR) for the detection of acute cardiac allograft rejection (ACAR).BackgroundACAR is currently diagnosed by endomyocardial biopsy, but CMR may be a noninvasive alternative because of its capacity for regional myocardial structure and function characterization.MethodsFifty-eight transplant recipients (mean age 47.0 ± 14.7 years) and 14 control subjects (mean age 47.7 ± 16.7 years) were prospectively recruited from August 2014 to May 2017 and underwent 97 CMR studies (83 transplant recipients, 14 control subjects) for assessment of global left ventricular function and myocardial T2, T1, and extracellular volume fraction (ECV). CMR studies were divided into 4 groups on the basis of biopsy grade: control subjects (n = 14), patients with no ACAR (no history of ACAR; n = 36), patients with past ACAR (history of ACAR; n = 24), and ACAR+ patients (active grade ≥1R ACAR; n = 23).ResultsMyocardial T2 was significantly higher in patients with past ACAR compared with those with no ACAR (51.0 ± 3.8 ms vs. 49.2 ± 4.0 ms; p = 0.02) and in patients with no ACAR compared with control subjects (49.2 ± 4.0 ms vs. 45.2 ± 2.3 ms; p < 0.01). ACAR+ patients demonstrated increased T2 compared with the no ACAR group (52.4 ± 4.7 ms vs. 49.2 ± 4.0 ms, p < 0.01) but not compared with the past ACAR group. In contrast, ECV was significantly elevated in ACAR+ patients compared with transplant recipients without ACAR regardless of history of ACAR (no ACAR: 31.5 ± 3.9% vs. 26.8 ± 3.3% [p < 0.01]; past ACAR: 31.5 ± 3.9% vs. 26.8 ± 4.0% [p < 0.01]). Receiver operating characteristic curve analysis revealed that a combined model of age at CMR, global T2, and global ECV was predictive of ACAR (area under the curve = 0.84).ConclusionsThe combination of CMR-derived myocardial T2 and ECV has potential as a noninvasive tissue biomarker for ACAR. Larger studies during acute ACAR are needed for continued development of multiparametric CMR for transplant recipient surveillance.     

Pericardial Fat and the Risk of Heart Failure

BackgroundObesity is a well-established risk factor for heart failure (HF). However, implications of pericardial fat on incident HF is unclear.ObjectivesThis study sought to examine the association between pericardial fat volume (PFV) and newly diagnosed HF.MethodsThis study ascertained PFV using cardiac computed tomography in 6,785 participants (3,584 women and 3,201 men) without pre-existing cardiovascular disease from the MESA (Multi-Ethnic Study of Atherosclerosis). Cox proportional hazards regression was used to evaluate PFV as continuous and dichotomous variable, maximizing the J-statistic: (Sensitivity + Specificity – 1).ResultsIn 90,686 person-years (median: 15.7 years; interquartile range: 11.7 to 16.5 years), 385 participants (5.7%; 164 women and 221 men) developed newly diagnosed HF. PFV was lower in women than in men (69 ± 33 cm³ vs. 92 ± 47 cm³; p < 0.001). In multivariable analyses, every 1-SD (42 cm³) increase in PFV was associated with a higher risk of HF in women (hazard ratio [HR]: 1.44; 95% confidence interval [CI]: 1.21 to 1.71; p < 0.001) than in men (HR: 1.13; 95% CI: 1.01 to 1.27; p = 0.03) (interaction p = 0.01). High PFV (≥70 cm³ in women; ≥120 cm³ in men) conferred a 2-fold greater risk of HF in women (HR: 2.06; 95% CI: 1.48 to 2.87; p < 0.001) and a 53% higher risk in men (HR: 1.53; 95% CI: 1.13 to 2.07; p = 0.006). In sex-stratified analyses, greater risk of HF remained robust with additional adjustment for anthropometric indicators of obesity (p ≤ 0.008), abdominal subcutaneous or visceral fat (p ≤ 0.03) or biomarkers of inflammation and hemodynamic stress (p < 0.001) and was similar among Whites, Blacks, Hispanics, and Chinese (interaction p = 0.24). Elevated PFV predominantly augmented the risk of HF with preserved ejection fraction (p < 0.001) rather than reduced ejection fraction (p = 0.31).ConclusionsIn this large, community-based, ethnically diverse, prospective cohort study, pericardial fat was associated with an increased risk of HF, particularly HF with preserved ejection fraction, in women and men.     

LA Mechanics in Decompensated Heart Failure: Insights From Strain Echocardiography With Invasive Hemodynamics

ObjectivesThe aim of this study was to assess the effect of congestion and decongestive therapy on left atrial (LA) mechanics and to determine the relationship between LA improvement after decongestive therapy and clinical outcome in immediate or chronic heart failure with reduced ejection fraction (HFrEF).BackgroundLA mechanics are affected by volume/pressure overload in decompensated HFrEF.MethodsA total of 31 patients with HFrEF and immediate heart failure (age 64 ± 15 years, 74% male, left ventricular ejection fraction 20 ± 12%) underwent serial echocardiography during decongestive therapy with simultaneous hemodynamic monitoring. LA function was assessed by strain (rate) imaging. Patients were re-evaluated 6 weeks after discharge and prospectively followed up for the composite endpoint of heart failure readmission and all-cause mortality.ResultsLA reservoir function was markedly reduced at baseline and improved with decongestion (peak atrial longitudinal strain from 6.4 ± 2.2% to 8.8 ± 3.0% and strain rate from 0.29 ± 0.11 s^–1 to 0.38 ± 0.13 s^–1), independent of changes in left ventricular global longitudinal strain, LA end-diastolic volume, and mitral regurgitation severity (p < 0.001). Both measures continued to rise at 6 weeks (up to 13.4 ± 6.1% and 0.50 ± 0.19 s^–1, respectively; p < 0.001). LA pump strain rate only increased 6 weeks after discharge (–0.25 ± 0.12 s^–1 to –0.55 ± 0.29 s^–1; p < 0.010). Changes in LA mechanics correlated with changes in wedge pressure (r = –0.61; p < 0.001). Lower peak atrial longitudinal strain values after decongestion were associated with increased risk for the composite endpoint of heart failure and mortality (p < 0.019).ConclusionsLA reservoir and booster function, while severely impaired during immediate decompensation, significantly improve during and after decongestive therapy. Poor LA reservoir function after decongestion is associated with worse outcome.     

Native T1 Mapping in the Diagnosis of Cardiac Allograft Rejection: A Prospective Histologically Validated Study

ObjectivesThis study aimed to determine the role of T₁ mapping in identifying cardiac allograft rejection.BackgroundEndomyocardial biopsy (EMBx), the current gold standard to diagnose cardiac allograft rejection, is associated with potentially serious complications. Cardiac magnetic resonance (CMR)–based T₁ mapping detects interstitial edema and fibrosis, which are important markers of acute and chronic rejection. Therefore, T₁ mapping can potentially diagnose cardiac allograft rejection noninvasively.MethodsPatients underwent CMR within 24 h of EMBx. T₁ maps were acquired at 1.5-T. EMBx-determined rejection was graded according to International Society of Heart and Lung Transplant (ISHLT) criteria.ResultsOf 112 biopsies with simultaneous CMR, 60 were classified as group 0 (ISHLT grade 0), 35 as group 1 (ISHLT grade 1R), and 17 as group 2 (2R, 3R, clinically diagnosed rejection, antibody-mediated rejection). Native T₁ values in patients with grade 0 biopsies and left ventricular ejection fraction >60% (983 ± 42 ms; 95% confidence interval: 972 to 994 ms) were comparable to values in nontransplant healthy control subjects (974 ± 45 ms; 95% confidence interval: 962 to 987 ms). T₁ values were significantly higher in group 2 (1,066 ± 78 ms) versus group 0 (984 ± 42 ms; p = 0.0001) and versus group 1 (1,001 ± 54 ms; p = 0.001). After excluding patients with an estimated glomerular filtration rate <50 ml/min/m², there was a moderate correlation of log-transformed native T₁ with high-sensitivity troponin T (r = 0.54, p < 0.0001) and pro–B-type natriuretic peptide (r = 0.67, p < 0.0001). Using a T₁ cutoff value of 1,029 ms, the sensitivity, specificity, and negative predictive value were 93%, 79%, and 99%, respectively.ConclusionsMyocardial tissue characterization with T₁ mapping displays excellent negative predictive capacity for the noninvasive detection of cardiac allograft rejection and holds promise to reduce substantially the EMBx requirement in cardiac transplant rejection surveillance.     

Regional Distribution of Fluorine-18-Flubrobenguane and Carbon-11-Hydroxyephedrine for Cardiac PET Imaging of Sympathetic Innervation

ObjectivesThe aim of this study was to investigate the regional distribution of novel ¹⁸F-labeled positron emission tomographic (PET) tracer flubrobenguane (FBBG) (whose longer half-life could enable more widespread use) to assess myocardial presynaptic sympathetic nerve function in humans in comparison to [¹¹C]meta-hydroxyephedrine (HED).BackgroundThe sympathetic nervous system (SNS) is vitally linked to cardiovascular regulation and disease. SNS imaging has shown prognostic value. HED is the most commonly used PET tracer for evaluation of sympathetic function in humans, but widespread clinical use is limited because of the short half-life of ¹¹C.MethodsA total of 25 participants (n = 6 healthy; n = 14 ischemic cardiomyopathy, left ventricular [LV] ejection fraction [EF] = 34 ± 5%; and n = 5 nonischemic cardiomyopathy, EF = 33 ± 3%) underwent 2 separate PET imaging visits 8.7 ± 7.6 days apart. On 1 visit, participants underwent dynamic HED PET imaging. On a different visit, participants underwent dynamic FBBG PET imaging. The order of testing was random. HED and FBBG global innervation (retention index [RI] and distribution volume [DV]) and regional denervation (% nonuniformity) were quantified to assess regional presynaptic sympathetic innervations.ResultsFBBG RI (r² = 0.72; ICC = 0.79; p < 0.0001), DV (r² = 0.62; ICC = 0.78; p < 0.0001), and regional denervation (r² = 0.97; ICC = 0.98; p < 0.0001) correlated highly with HED. Average LV RI values were highly similar between HED (7.3 ± 2.4%/min) and FBBG (7.0 ± 1.7%/min; p = 0.33). Post-hoc analysis did not reveal any between-tracer differences on a regional level (17-segment), suggesting equivalent regional distributions in both patients with and without ischemic cardiomyopathy.ConclusionsFBBG and HED yield equivalent global and regional distributions in both patients with and without ischemic cardiomyopathy. ¹⁸F-labeled PET tracers, such as FBBG, are critical for widespread distribution necessary for multicenter clinical trials and to maximize patient impact.     

Moderate Aortic Stenosis in Patients With Heart Failure and Reduced Ejection Fraction

BackgroundThe study investigators previously reported that moderate aortic stenosis (AS) is associated with a poor prognosis in patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF) (HFrEF). However, the respective contribution of moderate AS versus HFrEF to the outcomes of these patients is unknown.ObjectivesThis study sought to determine the impact of moderate AS on outcomes in patients with HFrEF.MethodsThe study included 262 patients with moderate AS (aortic valve area >1.0 and <1.5 cm²; and peak aortic jet velocity >2 and <4 m/s, at rest or after dobutamine stress echocardiography) and HFrEF (LVEF <50%). These patients were matched 1:1 for sex, age, estimated glomerular filtration rate, New York Heart Association functional class III to IV, presence of diabetes, LVEF, and body mass index with patients with HFrEF but no AS (i.e., peak aortic jet velocity <2 m/s). The endpoints were all-cause mortality and the composite of death and HF hospitalization.ResultsA total of 262 patients with HFrEF and moderate AS were matched with 262 patients with HFrEF and no AS. Mean follow-up was 2.9 ± 2.2 years. In the moderate AS group, mean aortic valve area was 1.2 ± 0.2 cm², and mean gradient was 14.5 ± 4.7 mm Hg. Moderate AS was associated with an increased risk of mortality (hazard ratio [HR]: 2.98; 95% confidence interval [CI]: 2.08 to 4.31; p < 0.0001) and of the composite of HF hospitalization and mortality (HR: 2.34; 95% CI: 1. 72 to 3.21; p < 0.0001). In the moderate AS group, aortic valve replacement (AVR) performed in 44 patients at a median follow-up time of 10.9 ± 16 months during follow-up was associated with improved survival (HR: 0.59; 95% CI: 0.35 to 0.98; p = 0.04). Notably, surgical AVR was not significantly associated with improved survival (p = 0.92), whereas transcatheter AVR was (HR: 0.43; 95% CI: 0.18 to 1.00; p = 0.05).ConclusionsIn this series of patients with HFrEF, moderate AS was associated with a marked incremental risk of mortality. AVR, and especially transcatheter AVR during follow-up, was associated with improved survival in patients with HFrEF and moderate AS. These findings provide support to the realization of a randomized trial to assess the effect of early transcatheter AVR in patients with HFrEF and moderate AS.     

Transcatheter Replacement of Transcatheter Versus Surgically Implanted Aortic Valve Bioprostheses

BackgroundSurgical aortic valve replacement and transcatheter aortic valve replacement (TAVR) are now both used to treat aortic stenosis in patients in whom life expectancy may exceed valve durability. The choice of initial bioprosthesis should therefore consider the relative safety and efficacy of potential subsequent interventions.ObjectivesThe aim of this study was to compare TAVR in failed transcatheter aortic valves (TAVs) versus surgical aortic valves (SAVs).MethodsData were collected on 434 TAV-in-TAV and 624 TAV-in-SAV consecutive procedures performed at centers participating in the Redo-TAVR international registry. Propensity score matching was applied, and 330 matched (165:165) patients were analyzed. Principal endpoints were procedural success, procedural safety, and mortality at 30 days and 1 year.ResultsFor TAV-in-TAV versus TAV-in-SAV, procedural success was observed in 120 (72.7%) versus 103 (62.4%) patients (p = 0.045), driven by a numerically lower frequency of residual high valve gradient (p = 0.095), ectopic valve deployment (p = 0.081), coronary obstruction (p = 0.091), and conversion to open heart surgery (p = 0.082). Procedural safety was achieved in 116 (70.3%) versus 119 (72.1%) patients (p = 0.715). Mortality at 30 days was 5 (3%) after TAV-in-TAV and 7 (4.4%) after TAV-in-SAV (p = 0.570). At 1 year, mortality was 12 (11.9%) and 10 (10.2%), respectively (p = 0.633). Aortic valve area was larger (1.55 ± 0.5 cm² vs. 1.37 ± 0.5 cm²; p = 0.040), and the mean residual gradient was lower (12.6 ± 5.2 mm Hg vs. 14.9 ± 5.2 mm Hg; p = 0.011) after TAV-in-TAV. The rate of moderate or greater residual aortic regurgitation was similar, but mild aortic regurgitation was more frequent after TAV-in-TAV (p = 0.003).ConclusionsIn propensity score–matched cohorts of TAV-in-TAV versus TAV-in-SAV patients, TAV-in-TAV was associated with higher procedural success and similar procedural safety or mortality.     

Cardiac Involvement in Patients Recovered From COVID-2019 Identified Using Magnetic Resonance Imaging

ObjectivesThis study evaluated cardiac involvement in patients recovered from coronavirus disease-2019 (COVID-19) using cardiac magnetic resonance (CMR).BackgroundMyocardial injury caused by COVID-19 was previously reported in hospitalized patients. It is unknown if there is sustained cardiac involvement after patients’ recovery from COVID-19.MethodsTwenty-six patients recovered from COVID-19 who reported cardiac symptoms and underwent CMR examinations were retrospectively included. CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping). Edema ratio and LGE were assessed in post–COVID-19 patients. Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls.ResultsFifteen patients (58%) had abnormal CMR findings on conventional CMR sequences: myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients. Decreased right ventricle functional parameters including ejection fraction, cardiac index, and stroke volume/body surface area were found in patients with positive conventional CMR findings. Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly elevated in patients with positive conventional CMR findings, compared with patients without positive findings and controls (median [interquartile range]: native T1 1,271 ms [1,243 to 1,298 ms] vs. 1,237 ms [1,216 to 1,262 ms] vs. 1,224 ms [1,217 to 1,245 ms]; mean ± SD: T2 42.7 ± 3.1 ms vs. 38.1 ms ± 2.4 vs. 39.1 ms ± 3.1; median [interquartile range]: 28.2% [24.8% to 36.2%] vs. 24.8% [23.1% to 25.4%] vs. 23.7% [22.2% to 25.2%]; p = 0.002; p < 0.001, and p = 0.002, respectively).ConclusionsCardiac involvement was found in a proportion of patients recovered from COVID-19. CMR manifestation included myocardial edema, fibrosis, and impaired right ventricle function. Attention should be paid to the possible myocardial involvement in patients recovered from COVID-19 with cardiac symptoms.     

5-Year Outcomes After TAVR With Balloon-Expandable Versus Self-Expanding Valves: Results From the CHOICE Randomized Clinical Trial

ObjectivesThe purpose of this study was to evaluate clinical and echocardiographic outcome data of the CHOICE (Randomized Comparison of Transcatheter Heart Valves in High Risk Patients with Severe Aortic Stenosis: Medtronic CoreValve Versus Edwards SAPIEN XT) trial at 5 years.BackgroundThe CHOICE trial was designed to compare device performance of a balloon-expandable (BE) transcatheter heart valve (THV) versus a self-expanding (SE) THV.MethodsThe CHOICE trial is an investigator-initiated trial that randomized 241 high-risk patients with severe symptomatic aortic stenosis and an anatomy suitable for treatment with both BE and SE THVs to transfemoral transcatheter aortic valve replacement with either device. The primary endpoint was device success. Patients were followed up to 5 years, with assessment of clinical outcomes, and echocardiographic evaluation of valve function and THV durability.ResultsAfter 5 years, there were no statistically significant differences between BE and SE valves in the cumulative incidence of death from any cause (53.4% vs. 47.6%; p = 0.38), death from cardiovascular causes (31.6% vs. 21.5%; p = 0.12), all strokes (17.5% vs. 16.5%; p = 0.73), and repeat hospitalization for heart failure (28.9% vs. 22.5%; p = 0.75). SE patients had larger prosthetic valve area (1.6 ± 0.5 cm² vs. 1.9 ± 0.5 cm²; p = 0.02) with a lower mean transprosthetic gradient (12.2 ± 8.7 mm Hg vs. 6.9 ± 2.7 mm Hg; p = 0.001) at 5 years. No differences were observed in the rates of paravalvular regurgitation. Clinical valve thrombosis occurred in 7 BE patients (7.3%) and 1 SE patient (0.8%; p = 0.06), and moderate or severe structural valve deterioration in 6 BE patients (6.6%) and no SE patient (0%; p = 0.018). The rate of bioprosthetic valve failure was low and not significantly different between both groups (4.1% vs. 3.4%; p = 0.63).ConclusionsFive-year follow-up of patients in the CHOICE trial revealed clinical outcomes after transfemoral transcatheter aortic valve replacement with early-generation BE and SE valves that were not statistically significantly different, with limited statistical power. Forward flow hemodynamics were significantly better with the SE valve. Moderate or severe structural valve deterioration was uncommon but occurred more frequently with the BE valve. (A Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: The CHOICE Trial [CHOICE]; NCT01645202)     

Additional Prognostic Value of 2D Right Ventricular Speckle-Tracking Strain for Prediction of Survival in Heart Failure and Reduced Ejection Fraction: A Comparative Study With Cardiac Magnetic Resonance

ObjectivesThis study sought to compare the prognostic value of 2-dimensional (2D) right ventricular (RV) speckle tracking (STE) against cardiac magnetic resonance (CMR) RV ejection fraction (EF) and feature tracking (FT) and conventional echocardiographic parameters on overall and cardiovascular (CV) survival in patients with heart failure with reduced EF (HFrEF).BackgroundPrior works showed that RV systolic function predicts prognosis in HFrEF. 2D RVSTE had recently been proposed as new echocardiographic method to evaluate RV dysfunction.MethodsA total of 266 patients with HFrEF (mean LVEF 23 ± 7%, 60 ± 14 years of age; 29% women) underwent RV function assessment using CMR and 2D echocardiography and were followed for a primary endpoint of overall death and secondary endpoint of CV death.ResultsAverage CMR-RVEF was 42 ± 15%, average STE RV global longitudinal strain (STE-RVGLS) was −18.0 ± 4.9%, and average CMR-FT-RVGLS was −11.8 ± 4.3%. After a median follow-up of 4.7 years, 102 patients died, 84 of a CV cause. RVEF, FT-RVGLS, tricuspid annulus plane systolic excursion (TAPSE), fractional area change (FAC), and STE-RVGLS were significant univariate predictors of overall and cardiac death. In multivariate Cox regression, age, ischemic etiology, diabetes, New York Heart Association functional class III to IV, and beta-blocker treatment were independent clinical predictors of overall mortality. CMR-RVEF (chi-square to enter = 3.9; p < 0.05), FT-RVGLS (chi-square to enter 3.7; p = 0.05), FAC (chi-square to enter 6.2; p = 0.02), and TAPSE (chi-square to enter = 4.1; p = 0.04) provided additional prognostic value over these baseline parameters, but the additional predictive value of STE-RVGLS (chi-square to enter = 10.8; p < 0.001) was significantly (p < 0.05) higher than the other tests. Additional hazard ratio to predict overall mortality was 2.5 (95% confidence interval [CI]: 1.6 to 3.9) for STE-RVGLS <−19%, 2.15 (95% CI: 1.34 to 3.43) for TAPSE >15 mm, 1.6 (95% CI: 1.02 to 2.49) for FAC >39%, 1.93 (95% CI: 1.25 to 2.99) for RVEF >41%, and 1.87 (95% CI: 1.10 to 3.19) for CMR-FT-RVGLS <−15%.Conclusions2D RVGLS provides strong additional prognostic value to predict overall and CV mortality in HFrEF, with higher predictive value than CMR-RVEF, CMR-FT-RVGLS, TAPSE, or FAC. This supports use of STE-RVGLS to identify higher-risk HFrEF patients.     

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor–Associated Myocarditis

BackgroundMyocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.ObjectivesThis study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.MethodsIn this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.ResultsOf 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE.ConclusionsThe use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.     

Outcomes of TTVI in Patients With Pacemaker or Defibrillator Leads: Data From the TriValve Registry

ObjectivesThe interference of a transtricuspid cardiac implantable electronic device (CIED) lead with tricuspid valve function may contribute to the mechanism of tricuspid regurgitation (TR) and poses specific therapeutic challenges during transcatheter tricuspid valve intervention (TTVI). Feasibility and efficacy of TTVI in presence of a CIED is unclear.BackgroundFeasibility of TTVI in presence of a CIED lead has never been proven on a large basis.MethodsThe study population consisted of 470 patients with severe symptomatic TR from the TriValve (Transcatheter Tricuspid Valve Therapies) registry who underwent TTVI at 21 centers between 2015 and 2018. The association of CIED and outcomes were assessed.ResultsPre-procedural CIED was present in 121 of 470 (25.7%) patients. The most frequent location of the CIED lead was the posteroseptal commissure (44.0%). As compared with patients without a transvalvular lead (no-CIED group), patients having a tricuspid lead (CIED group) were more symptomatic (New York Heart Association functional class III to IV in 95.9% vs. 92.3%; p = 0.02) and more frequently had previous episodes of right heart failure (87.8% vs. 69.0%; p = 0.002). No-CIED patients had more severe TR (effective regurgitant orifice area 0.7 ± 0.6 cm² vs. 0.6 ± 0.3 cm²; p = 0.02), but significantly better right ventricular function (tricuspid annular plane systolic excursion = 16.7 ± 5.0 mm vs. 15.9 ± 4.0 mm; p = 0.04). Overall, 373 patients (79%) were treated with the MitraClip (Abbott Vascular, Santa Clara, California) (106 [87.0%] in the CIED group). Among them, 154 (33%) patients had concomitant transcatheter mitral repair (55 [46.0%] in the CIED group, all MitraClip). Procedural success was achieved in 80.0% of no-CIED patients and in 78.6% of CIED patients (p = 0.74), with an in-hospital mortality of 2.9% and 3.7%, respectively (p = 0.70). At 30 days, residual TR ≤2+ was observed in 70.8% of no-CIED and in 73.7% of CIED patients (p = 0.6). Symptomatic improvement was observed in both groups (NYHA functional class I to II at 30 days: 66.0% vs. 65.0%; p = 0.30). Survival at 12 months was 80.7 ± 3.0% in the no-CIED patients and 73.6 ± 5.0% in the CIED patients (p = 0.30).ConclusionsTTVI is feasible in selected patients with CIED leads and acute procedural success and short-term clinical outcomes are comparable to those observed in patients without a transtricuspid lead.     

High-Risk Coronary Plaque Regression After Intensive Lifestyle Intervention in Nonobstructive Coronary Disease: A Randomized Study

ObjectivesThe authors sought to study the impact of diet and lifestyle intervention on changes in atherosclerotic plaque volume and composition.BackgroundLifestyle and diet modification are the leading strategies to manage coronary artery disease; however, their direct impact on atherosclerosis remains unknown. Coronary plaque composition is related to the risk of future cardiovascular events independent of stenosis severity and can be conveniently evaluated with computed tomography angiography (CTA).MethodsWe enrolled 92 patients (41% women; mean age 60 ± 7.7 years) with nonobstructive (<70% stenosis) coronary atherosclerosis identified by CTA. Participants were randomized (1:1) to either the DISCO (Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography) intervention group (systematic follow-up by a dietitian to adhere to the Dietary Approaches to Stop Hypertension nutrition model together with optimal medical therapy [OMT]) or the control group (OMT alone). In all patients, CTA was repeated after 66.9 ± 13.7 weeks. The outcome was change (Δ) in atheroma volume and plaque composition. Based on atherosclerotic tissue attenuation ranges in Hounsfield units (HU), the following components of coronary plaque were distinguished: dense calcium (>351 HU), fibrous plaque (151 to 350 HU), and fibrofatty plaque combined with necrotic core (-30 to 150 HU), referred to as noncalcified plaque.ResultsPercent atheroma volume increased in the control arm (Δ = +1.1 ± 3.4%; p = 0.033) versus no significant change in the experimental arm (Δ = +1.0% ± 4.2%; p = 0.127; intergroup p = 0.851). There was a reduction in noncalcified plaque in both the experimental arm (Δ = ?51.3 ± 79.5 mm³ [?1.7 ± 2.7%]; p < 0.001) and the control arm (Δ = ?21.3 ± 57.7 [?0.7 ± 1.9%]; p = 0.018), which was greater in the DISCO intervention group (intergroup p = 0.045). No differences in fibrous component or dense calcium changes were observed between the groups.ConclusionsControlled diet and lifestyle intervention together with OMT may slow the progression of atherosclerosis and reduce noncalcified plaque volume compared to OMT alone. (Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography [DISCO-CT]; NCT02571803)     

Insufficient Mitral Leaflet Remodeling in Relation to Annular Dilation and Risk of Residual Mitral Regurgitation After MitraClip Implantation

ObjectivesThe purpose of this study was to determine whether the mitral valve (MV) total leaflet area (TLA)-to-mitral annular area (MAA) (TLA/MAA) ratio measured using 3-dimensional (3D) transesophageal echocardiography (TEE) was associated with residual mitral regurgitation (MR) after MitraClip implantation in patients with secondary MR.BackgroundThe factors influencing the results of MitraClip implantation for secondary MR are controversial. This study hypothesized that insufficient remodeling of the mitral leaflets relative to the annular dilation may be associated with significant MR after MitraClip implantation.MethodsThis study included patients with secondary MR treated with MitraClips. Using 3D TEE dataset, the TLA in diastole and MAA in systole were measured with dedicated software.ResultsIn a total cohort of 119 patients (mean age 74 ± 9 years; 61% male), significant residual MR (≥2+) was present in 43 patients (36%). In patients with significant residual MR, MAA was greater than in patients without residual MR (10.7 ± 2.4 cm² vs. 9.0 ± 2.1 cm²; p < 0.001) whereas no significant difference was observed in TLA (12.2 ± 2.6 cm² vs. 12.0 ± 2.9 cm²; p = 0.836). TLA/MAA ratio was lower in patients with significant residual MR as compared to their counterparts (1.14 ± 0.15 vs. 1.34 ± 0.16; p < 0.001), suggesting insufficient leaflet remodeling relative to annular dilation. On receiver-operating characteristic curve analysis, the TLA/MAA ratio had better discriminative power to identify patients who will have significant residual MR compared to MAA alone (area under the curve [AUC]: 0.830 vs. 0.723; p = 0.049).ConclusionsIn patients with secondary MR, insufficient mitral leaflet remodeling relative to the annulus dilation, as reflected by a lower TLA/MAA ratio, is associated with significant residual MR after MitraClip implantation.     

Value of CMR and PET in Predicting Ventricular Arrhythmias in Ischemic Cardiomyopathy Patients Eligible for ICD

ObjectivesThis study presents a head-to-head comparison of the value of cardiac magnetic resonance (CMR)-derived left-ventricular (LV) function and scar burden and positron emission tomography (PET)-derived perfusion and innervation in predicting ventricular arrhythmias (VAs).BackgroundImproved risk stratification of VA is important to identify patients who should benefit of prophylactic implantable cardioverter-defibrillator (ICD) implantation. Perfusion abnormalities, sympathetic denervation, and scar burden have all been linked to VA, although comparative studies are lacking.MethodsSeventy-four patients with ischemic cardiomyopathy and left-ventricular ejection fraction (LVEF) ≤35%, referred for primary prevention ICD placement were enrolled prospectively. Late gadolinium-enhanced (LGE) CMR was performed to assess LV function and scar characteristics. [¹⁵O]H₂O and [¹¹C]hydroxyephedrine positron emission tomography (PET) were performed to quantify resting and hyperemic myocardial blood flow (MBF), coronary flow reserve (CFR), and sympathetic innervation. During follow-up of 5.4 ± 1.9 years, the occurrence of sustained VA, appropriate ICD therapy, and mortality were evaluated.ResultsIn total, 20 (26%) patients experienced VA. CMR and PET parameters showed considerable overlap between patients with VA and patients without VA, caused by substantial heterogeneity within groups. Univariable analyses showed that lower LVEF (hazard ratio [HR]: 0.92; p = 0.03), higher left-ventricular end-diastolic volume index (LVEDVi) (HR 1.02; p < 0.01), and larger scar border zone (HR 1.11; p = 0.03) were related to VA. Scar core size, resting MBF, hyperemic MBF, perfusion defect size, innervation defect size, and the innervation-perfusion mismatch were not found to be associated with VA.ConclusionsIn patients with ischemic cardiomyopathy, lower LVEF, higher LVEDVi, and larger scar border zone were related to VA. PET-derived perfusion and sympathetic innervation, as well as CMR-derived scar core size were not associated with VA. These results suggest that improved prediction of VA by advanced imaging remains challenging for the individual patient.     

Prognostic Value of Stress CMR Perfusion Imaging in Patients With Reduced Left Ventricular Function

ObjectivesThe aim of this study was to investigate the prognostic value of stress cardiac magnetic resonance imaging (CMR) in patients with reduced left ventricular (LV) systolic function.BackgroundPatients with ischemic cardiomyopathy are at risk from both myocardial ischemia and heart failure. Invasive testing is often used as the first-line investigation, and there is limited evidence as to whether stress testing can effectively provide risk stratification.MethodsIn this substudy of a multicenter registry from 13 U.S. centers, patients with reduced LV ejection fraction (<50%), referred for stress CMR for suspected myocardial ischemia, were included. The primary outcome was cardiovascular death or nonfatal myocardial infarction. The secondary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, hospitalization for unstable angina or congestive heart failure, and unplanned late coronary artery bypass graft surgery.ResultsAmong 582 patients (mean age 62 ± 12 years, 34% women), 40% had a history of congestive heart failure, and the median LV ejection fraction was 39% (interquartile range: 28% to 45%). At median follow-up of 5.0 years, 97 patients had experienced the primary outcome, and 182 patients had experienced the secondary outcome. Patients with no CMR evidence of ischemia or late gadolinium enhancement (LGE) experienced an annual primary outcome event rate of 1.1%. The presence of ischemia, LGE, or both was associated with higher event rates. In a multivariate model adjusted for clinical covariates, ischemia and LGE were independent predictors of the primary (hazard ratio [HR]: 2.63; 95% confidence interval [CI]: 1.68 to 4.14; p < 0.001; and HR: 1.86; 95% CI: 1.05 to 3.29; p = 0.03) and secondary (HR: 2.14; 95% CI: 1.55 to 2.95; p < 0.001; and HR 1.70; 95% CI: 1.16 to 2.49; p = 0.007) outcomes. The addition of ischemia and LGE led to improved model discrimination for the primary outcome (change in C statistic from 0.715 to 0.765; p = 0.02). The presence and extent of ischemia were associated with higher rates of use of downstream coronary angiography, revascularization, and cost of care spent on ischemia testing.ConclusionsStress CMR was effective in risk-stratifying patients with reduced LV ejection fractions. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891)