Unintended Deformation of Stents During Bifurcation PCI: An OCTOBER Trial Substudy.

BACKGROUND: Unintended deformation of implanted coronary stents can lead to loss of coronary access, stent thrombosis and coronary events during follow-up. The incidence, mechanisms and clinical outcomes of unintended stent deformations (USD) during complex bifurcation stenting are not well characterized. OBJECTIVES: In a prespecified analysis of the OCTOBER (European Trial on Optical Coherence Tomography Optimized Bifurcation Event Reduction) trial, we aimed to: 1) determine the incidence and characterize mechanisms of USD identified by optical coherence tomography (OCT); and 2) evaluate physician's detection and correction of accidental abluminal rewiring and USD. METHODS: OCT scans were analyzed for accidental abluminal rewiring and USD. When USD was identified, the plausible mechanism was determined by analysis of all procedural OCT scans and the corresponding angiograms. RESULTS: USD was identified by the core lab in 9.3% (55/589) of OCT-guided cases. Accidental abluminal rewiring was the cause in 44% (24/55), and guide catheter collision was the cause in 40% (22/55) of cases. USD was found in 18.5% of all cases with left main bifurcation percutaneous coronary intervention. The total incidence of abluminal rewiring was 33 in 32 OCT-guided cases (5.4%) and was corrected by physicians in 18 of 33 appearances (54.5%). The 2-year major adverse cardiac event rate for patients with untreated USD (n = 30) was 23.3%, whereas patients with confirmed or possibly corrected USD (n = 25) had no events during follow-up. CONCLUSIONS: USD was associated with adverse procedural complications and cardiac events during follow-up when not identified and corrected. The predominant mechanisms were undetected abluminal rewiring and guide catheter collision. Left main bifurcation percutaneous coronary intervention was a particular risk with USD detected in 18.5% of cases.

OCT or Angiography Guidance for PCI in Complex Bifurcation Lesions.

BACKGROUND: Imaging-guided percutaneous coronary intervention (PCI) is associated with better clinical outcomes than angiography-guided PCI. Whether routine optical coherence tomography (OCT) guidance in PCI of lesions involving coronary-artery branch points (bifurcations) improves clinical outcomes as compared with angiographic guidance is uncertain. METHODS: We conducted a multicenter, randomized, open-label trial at 38 centers in Europe. Patients with a clinical indication for PCI and a complex bifurcation lesion identified by means of coronary angiography were randomly assigned in a 1:1 ratio to OCT-guided PCI or angiography-guided PCI. The primary end point was a composite of major adverse cardiac events (MACE), defined as death from a cardiac cause, target-lesion myocardial infarction, or ischemia-driven target-lesion revascularization at a median follow-up of 2 years. RESULTS: We assigned 1201 patients to OCT-guided PCI (600 patients) or angiography-guided PCI (601 patients). A total of 111 patients (18.5%) in the OCT-guided PCI group and 116 (19.3%) in the angiography-guided PCI group had a bifurcation lesion involving the left main coronary artery. At 2 years, a primary end-point event had occurred in 59 patients (10.1%) in the OCT-guided PCI group and in 83 patients (14.1%) in the angiography-guided PCI group (hazard ratio, 0.70; 95% confidence interval, 0.50 to 0.98; P = 0.035). Procedure-related complications occurred in 41 patients (6.8%) in the OCT-guided PCI group and 34 patients (5.7%) in the angiography-guided PCI group. CONCLUSIONS: Among patients with complex coronary-artery bifurcation lesions, OCT-guided PCI was associated with a lower incidence of MACE at 2 years than angiography-guided PCI. (Funded by Abbott Vascular and others; OCTOBER ClinicalTrials.gov number, NCT03171311.).

Long-term changes in coronary physiology after aortic valve replacement.

BACKGROUND: The detrimental effects of long-standing severe aortic stenosis (AS) often include left ventricular hypertrophy (LVH) and exhaustion of coronary flow reserve (CFR), the reversibility of which is unclear after valve replacement. AIMS: Our aims were to 1) investigate whether CFR in the left anterior descending artery (LAD) would improve following valve replacement, and if the change was related to changes in hyperaemic coronary flow (QLAD) and minimal microvascular resistance (Rµ,LAD); and 2) investigate the relationship between changes in CFR and changes in left ventricular mass (LVM) and stroke work (LVSW). METHODS: We measured intracoronary bolus thermodilution-derived CFR, and continuous thermodilution-derived QLAD and Rµ,LAD before and 6 months after aortic valve replacement. Cardiac magnetic resonance imaging was used to quantify left ventricular anatomy and function for the calculation of LVM and LVSW.  Results: Thirty-four patients were included (17 patients had transcatheter aortic valve implantation; 14 had surgical valve replacement with a bioprosthesis and 3 with a mechanical prosthesis) who underwent invasive assessment in the LAD. CFR increased from 2.5 (interquartile range [IQR] 1.5-3.3) at baseline to 3.1 (IQR 2.2-5.1) at follow-up (p=0.005), despite no significant change in QLAD (230±106 mL/min to 250±101 mL/min; p=0.26) or Rµ,LAD (347 [IQR 247-463] to 287 [IQR 230-456]; p=0.20). When indexed for LVM, QLAD was 39% (IQR 8-98%) higher at follow-up compared with baseline (p<0.001). The improvement in CFR was correlated with ΔLVSW, r= -0.39; p=0.047.   Conclusions: CFR in the LAD increased significantly at follow-up although global hyperaemic flow and minimal microvascular resistance remained unchanged. Thus, a decrease in resting flow was the cause of CFR improvement. CFR improvement was associated with reduction in LVSW.

Echocardiographic Characterization of a Murine Model of Hypertrophic Obstructive Cardiomyopathy Induced by Cardiac-specific Overexpression of Epidermal Growth Factor Receptor 2.

Although rare, hypertrophic cardiomyopathy (HCM) with midventricular obstruction is often associated with severe symptoms and complications. None of the existing HCM animal models display this particular phenotype. Our group developed a mouse line that overexpresses the ErbB2 receptor (ErbB2(tg)) in cardiomyocytes; we previously showed that the ErbB2 receptor induces cardiomyocyte hypertrophy, myocyte disarray, and fibrosis compatible with HCM. In the current study, we sought to further echocardiographically characterize the ErbB2(tg) mouse line as a model of HCM. Compared with their wild-type littermates, ErbB2(tg) mice show increased left ventricular (LV) mass, concentric LV hypertrophy, and papillary muscle hypertrophy. This hypertrophy was accompanied by diastolic dysfunction, expressed as reduced E:A ratio, prolonged deceleration time, and elevated E:e' ratio. In addition, ErbB2(tg) mice consistently showed midcavity obstruction with elevated LV gradients, and the flow profile revealed a prolonged pressure increase and a delayed peak, indicating dynamic obstruction. The ejection fraction was increased in ErbB2(tg) mice, due to reduced end-diastolic and end-systolic LV volumes. Furthermore, systolic radial strain and systolic radial strain rate but not systolic circumferential strain and longitudinal strain were decreased in ErbB2(tg) compared with wild-type mice. In conclusion, the phenotype of the ErbB2(tg) mouse model is consistent with midventricular HCM in many important aspects, including massive LV hypertrophy, diastolic dysfunction, and midcavity obstruction. This pattern is unique for a small animal model, suggesting that ErbB2(tg) mice may be well suited for research into the hemodynamics and treatment of this rare form of HCM.

Choice of Treatment for Aortic Valve Stenosis in the Era of Transcatheter Aortic Valve Replacement in Eastern Denmark (2005 to 2015).

OBJECTIVES: The aim of this study was to evaluate the choice of treatment for severe aortic valve stenosis in the era of transcatheter aortic valve replacement (TAVR) in Eastern Denmark. BACKGROUND: Until the early 21st century, the only therapeutic option for aortic valve stenosis was surgical aortic valve replacement (SAVR), but this has changed with the introduction of TAVR. METHODS: Using the East Denmark Heart Registry, the evolution of AVR over time was studied for the period 2005 to 2015. RESULTS: TAVR has since its introduction in 2007 seen steady growth, with currently more than 35% of AVR procedures-and 45% of isolated AVR procedures-being performed by transcatheter-based technology. The number of SAVR procedures remained rather stable over the study period and even saw a slight decline since 2012-there was a marked decrease in the age at which surgical bioprostheses are considered appropriate. The age profile of TAVR patients remained unchanged over the study period, with a recent trend toward more low- and intermediate-risk patients. Currently, patients age ≥80 years and/or with a Society of Thoracic Surgeons (STS) surgical risk score >6 are automatically referred for TAVR, and one-half of patients age 70 to 80 years with an STS risk score of 4 to 6 are treated with TAVR. CONCLUSIONS: The number of TAVR procedures has increased steadily in recent years, with a TAVR penetration rate of 35% in 2015 and close to 45% when considering isolated AVR. The number of SAVR procedures remained stable over the study period, and surgical bioprostheses are currently used at a much younger age than in 2005.

Comparison of Clinical Features in Blacks Versus Whites With Hypertrophic Cardiomyopathy.

To date, there has not been a large systematic examination of the hypertrophic cardiomyopathy (HC) phenotype in blacks versus whites. In this study, we investigate differences in presentation of HC between blacks and whites. We included 441 consecutive patients with HC seen at the Johns Hopkins HC clinic in the period from February 2005 to June 2012. We compared 76 blacks for clinical presentation, electrocardiogram, exercise capacity, left ventricular morphology, and hemodynamics by echocardiography to 365 whites. Black patients with HC more often presented with abnormal electrocardiogram (93% vs 80%, p = 0.009), driven by a significant difference in repolarization abnormalities (79% vs 56%, p <0.001). Apical hypertrophy was more common in blacks (26% vs 9%, p <0.001); however, blacks had less severe systolic anterior movement of the mitral valve and had significantly lower left ventricular outflow tract gradients at rest (9 mm Hg; interquartile range [IQR] 7 to 19 vs 16 mm Hg; IQR 8 to 40, p <0.001) and during provocation (36 mm Hg; IQR 16 to 77 vs 59 mm Hg; IQR 26 to 110, p = 0.002). Despite the nonobstructive pathophysiology, blacks had lower exercise capacity (adjusted difference 1.45 metabolic equivalents [0.45 to 2.45], p = 0.005). In conclusion, blacks have an HC phenotype characterized by lower prevalence of the well-recognized echocardiographic features of HC such as systolic anterior movement of the mitral valve and left ventricular outflow tract obstruction and display worse exercise capacity.

Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves.

BACKGROUND: A finding of reduced aortic-valve leaflet motion was noted on computed tomography (CT) in a patient who had a stroke after transcatheter aortic-valve replacement (TAVR) during an ongoing clinical trial. This finding raised a concern about possible subclinical leaflet thrombosis and prompted further investigation. METHODS: We analyzed data obtained from 55 patients in a clinical trial of TAVR and from two single-center registries that included 132 patients who were undergoing either TAVR or surgical aortic-valve bioprosthesis implantation. We obtained four-dimensional, volume-rendered CT scans along with data on anticoagulation and clinical outcomes (including strokes and transient ischemic attacks [TIAs]). RESULTS: Reduced leaflet motion was noted on CT in 22 of 55 patients (40%) in the clinical trial and in 17 of 132 patients (13%) in the two registries. Reduced leaflet motion was detected among patients with multiple bioprosthesis types, including transcatheter and surgical bioprostheses. Therapeutic anticoagulation with warfarin, as compared with dual antiplatelet therapy, was associated with a decreased incidence of reduced leaflet motion (0% and 55%, respectively, P=0.01 in the clinical trial; and 0% and 29%, respectively, P=0.04 in the pooled registries). In patients who were reevaluated with follow-up CT, restoration of leaflet motion was noted in all 11 patients who were receiving anticoagulation and in 1 of 10 patients who were not receiving anticoagulation (P<0.001). There was no significant difference in the incidence of stroke or TIA between patients with reduced leaflet motion and those with normal leaflet motion in the clinical trial (2 of 22 patients and 0 of 33 patients, respectively; P=0.16), although in the pooled registries, a significant difference was detected (3 of 17 patients and 1 of 115 patients, respectively; P=0.007). CONCLUSIONS: Reduced aortic-valve leaflet motion was shown in patients with bioprosthetic aortic valves. The condition resolved with therapeutic anticoagulation. The effect of this finding on clinical outcomes including stroke needs further investigation. (Funded by St. Jude Medical and Cedars-Sinai Heart Institute; Portico-IDE ClinicalTrials.gov number, NCT02000115; SAVORY registry, NCT02426307; and RESOLVE registry, NCT02318342.).

Comparison of dyssynchrony parameters for VV-optimization in CRT patients.

BACKGROUND: Optimization of the interventricular delay (VV-optimization) in cardiac resynchronization therapy (CRT) patients can be performed by evaluation of mechanical dyssynchrony. However, there is no consensus on which method to use. In this study, three conceptually different methods were evaluated. METHODS: Thirty consecutive CRT patients were included. At day 1, patients were atrioventricular and VV optimized by left ventricular outflow tract (LVOT) velocity time integral (VTI). At 6 months, 2D strain (2DS) echocardiography and tissue Doppler imaging (TDI) was performed at six different VV-programming delay in steps of 20 ms. LVOT and three indices of dyssynchrony were evaluated at each setting: standard deviation (SD) of time-to-peak strain in 12 segments (2DS-SD), SD of time-to-peak velocities in 12 segments (TDI-SD), and maximal activation delay (AD-max) by cross-correlation analysis (XCA) of TDI-derived myocardial acceleration curves. RESULTS: Feasibility was 90% for 2DS-SD and TDI-SD and 97% for AD-max. Coefficients of variation for intraobserver variability were 13% for 2DS-SD, 11% for TDI-SD, and 6% for AD-max. A relative increase in LVOT VTI > 10% was observed in 5/12 (42%) nonresponders and 7/18 (39%) responders to CRT. Optimization by all three dyssynchrony indices significantly increased LVOT VTI compared to simultaneous pacing and optimal setting at day 1 (P < 0.05, all). LVOT VTI was highest when using AD-max, and AD-max showed the best agreement (k = 0.71). CONCLUSION: VV optimization at 6 months acutely benefits both responders and nonresponders; however, dyssynchrony indices do not perform equally well. XCA has a high feasibility and reproducibility and appears to be superior to time-to-peak techniques.

Variability of global left ventricular deformation analysis using vendor dependent and independent two-dimensional speckle-tracking software in adults.

BACKGROUND: Evaluation of myocardial deformation by two-dimensional speckle-tracking is useful for clinical and research purposes. However, differences may exist among different ultrasound machines, software packages, frame rates, and observers. METHODS: Thirty patients underwent echocardiography on both GE (Vivid 9; GE Vingmed Ultrasound AS, Horten, Norway) and Philips (iE33; Philips Ultrasound, Bothell, WA) ultrasound systems. From each study, two sets of images were stored in Digital Imaging and Communications in Medicine format, optimized for strain evaluation: one set of images at the acquisition frame rate (55-90 frames/sec) and one set of images at a compressed frame rate of 30 frames/sec. Vendor-independent software (VIS; TomTec 2D Cardiac Performance Analysis, Munich, Germany) was used to measure strain in multiple directions and was compared with vendor-specific software (GE EchoPAC; GE Vingmed Ultrasound AS). RESULTS: Intraobserver and interobserver coefficients of variation ranged from 5.5% to 8.7% for longitudinal strain, from 10.7% to 20.8% for circumferential, and from 15.3% to 33.4% for radial and transverse strain. Strain values obtained using VIS were comparable with those obtained using vendor-specific software for longitudinal strain, regardless of ultrasound machine or frame rate. For circumferential strain, a consistent large bias was observed between VIS and vendor-specific software, with higher values using VIS. Slightly higher strain values were observed by analysis at the acquisition frame rate compared with the low frame rate, but no consistent bias was observed between images from different vendors. CONCLUSIONS: Global longitudinal strain consistently showed good reproducibility, while reproducibility was moderate for circumferential strain and poor in the radial direction. Retrospective analysis of legacy Digital Imaging and Communications in Medicine data at 30 frames/sec can be reliably performed for longitudinal strain.

New approach to intracardiac hemodynamic measurements in small animals: echo-guided percutaneous apical puncture.

OBJECTIVES: Invasive measurements of intracardiac hemodynamics in animal models have allowed important advances in the understanding of cardiac disease. Currently they are performed either through a carotid arteriotomy or via a thoracotomy and apical insertion. Both of these techniques have disadvantages and are not conducive to repeated measurements. Therefore, the purpose of this study was to develop a new technique for measuring intracardiac hemodynamics. METHODS: In 13 male rats, hemodynamic measurements were performed using a new echocardiographically guided percutaneous apical technique. An intravenous catheter was percutaneously inserted into the left ventricle (LV) in the direction of the LV long axis. Through this catheter, a micromanometer-tipped pressure catheter was inserted, and invasive hemodynamic traces were recorded. After LV recordings, the pressure catheter was advanced into the aorta where pressures were obtained. In 11 rats, measurements were repeated after 1 week (n = 2), 2 weeks (n = 4), 3 weeks (n = 4), or 4 weeks (n = 1). In 3 rats, invasive measurements were performed using a carotid arteriotomy before the percutaneous technique. RESULTS: Among the 13 rats subjected to the procedure, the survival rate was 85%. Of the 11 rats that had the procedure repeated, 3 died (27%). The mean differences ± SD when comparing the two techniques were 10 ± 4 mm Hg for the LV end-systolic pressure and 1 ± 1 mm Hg for the LV end-diastolic pressure. The mean procedure times were 21 ± 3 and 6 ± 1 minutes for the carotid and percutaneous techniques, respectively. CONCLUSIONS: We have successfully developed a percutaneous technique for insertion of LV microtip catheters in rats.

Simple regional strain pattern analysis to predict response to cardiac resynchronization therapy: rationale, initial results, and advantages.

BACKGROUND: A classical strain pattern of early contraction in one wall and prestretching of the opposing wall followed by late contraction has previously been associated with left bundle branch block (LBBB) activation and short-term response to cardiac resynchronization therapy (CRT). Aims of this study were to establish the long-term predictive value of an LBBB-related strain pattern and to identify changes in contraction patterns during short-term and long-term CRT. METHODS AND RESULTS: Sixty-seven patients with standard CRT criteria were prospectively enrolled between early 2009 and late 2010. Echocardiography including regional strain analysis by 2-dimensional speckle tracking was performed 1 week before implantation, at day 1, and 6 months after. Response was defined as a decrease in left ventricular end-systolic volume ≥ 15%. The predictive ability of a classical pattern was compared with time-to-peak measurements from velocity and deformation analysis. Forty-three patients (65%) were classified as responders. The presence of a classical pattern showed 91% specificity and 95% sensitivity for response and performed significantly better than time-to-peak parameters in prediction of response to CRT (P < .001, all). In responders, CRT acutely increased septal longitudinal peak systolic strain (-8.7% ± 3.6% to -11.1% ± 3%, P < .001) but not in nonresponders. CONCLUSIONS: The classical pattern is highly predictive of response to CRT and superior to time-to-peak methods. Patients who obtain long-term reverse remodeling are characterized by short-term reversal of the classical strain pattern. These findings emphasize the value of recognizing potentially reversible strain patterns in selection of CRT candidates.

Preclinical systolic and diastolic dysfunction assessed by tissue Doppler imaging is associated with elevated plasma pro-B-type natriuretic peptide concentrations.

BACKGROUND: Heart failure is a major public health problem. To improve its grave prognosis, early identification of cardiac dysfunction is mandatory. Conventional echocardiography is not suitable for this. Tissue Doppler imaging (TDI), however, could be so. METHODS AND RESULTS: Within a large community-based population-study (n = 1012), cardiac function was evaluated by conventional echocardiography (left ventricular hypertrophy, dilatation, systolic, and severe diastolic dysfunction), TDI, and plasma proBNP. Averages of peak systolic (s'), early diastolic (e'), and late diastolic (a') velocities from 6 mitral annular sites were used. TDI was furthermore quantified by a combined index (eas-index) of diastolic and systolic performance: e'/(a' x s'). Compared with controls, persons with elevated plasma proBNP concentrations (n = 100) displayed lower systolic and diastolic performance by TDI, in terms of lower s' (P = 0.017) and a' (P < .001), and higher e'/a' (P = .002) and eas-index (P < .001). This pattern remained significant after multivariable adjustment for age, sex, body mass index, heart rate, estimated glomerular filtration rate, hypertension, diabetes, ischemic heart disease, and conventional echocardiography. Furthermore, TDI provided incremental information over conventional echocardiography in predicting elevated plasma proBNP concentrations. CONCLUSIONS: Preclinical systolic and diastolic dysfunction by TDI is associated with elevated plasma proBNP levels, even when conventional echocardiography is normal.

Cardiac dysfunction assessed by echocardiographic tissue Doppler imaging is an independent predictor of mortality in the general population.

BACKGROUND: Tissue Doppler imaging (TDI) detects left ventricular dysfunction in patients with heart failure and normal ejection fraction, but the prognostic significance of left ventricular dysfunction by TDI in the general population is unknown. METHODS AND RESULTS: Within the Copenhagen City Heart Study, a large community-based population study, cardiac function was evaluated in 1036 participants by both conventional echocardiography and TDI. Averages of peak systolic (s'), early diastolic (e'), and late diastolic (a') velocities from 6 mitral annular sites were used. TDI was furthermore quantified by a combined index (eas index) of diastolic and systolic performance: e'/(a' x s'). During follow-up (median, 5.3 years), 90 participants died. Left ventricular dysfunction by TDI, in terms of low s' (hazard ratio, 1.23 per 1-cm/s decrease; P<0.05) and a' (hazard ratio, 1.20 per 1-cm/s decrease; P=0.001), were significant predictors of death in Cox proportional-hazards models adjusted for clinical variables (age, sex, body mass index, heart rate, hypertension, diabetes mellitus, and ischemic heart disease) and conventional echocardiography. The adjusted hazard ratio for death in the third tertile compared with the first tertile of the combined index of systolic and diastolic performance by TDI was 2.5 (P<0.005). CONCLUSIONS: In the general population, in which most are free of left ventricular systolic dysfunction and restrictive diastolic filling using conventional echocardiographic parameters, left ventricular dysfunction by TDI is a powerful and independent predictor of death, especially when systolic performance and diastolic performance are considered together, recognizing their interdependency and their complex relation to deteriorating cardiac function.

Tissue Doppler echocardiography in persons with hypertension, diabetes, or ischaemic heart disease: the Copenhagen City Heart Study.

AIMS: To test the hypothesis that echocardiographic tissue Doppler imaging (TDI) reveals reduced myocardial function in hypertension, diabetes, and ischaemic heart disease (IHD) in the general population. METHODS AND RESULTS: Within a large, community-based population study, cardiac function was evaluated in 1036 participants by both conventional echocardiography and colour TDI. Peak systolic (s') and early diastolic (e') velocities, longitudinal displacement (LD), and the ratio of mitral inflow E-wave to e' (E/e') were measured. TDI revealed significantly impaired parameters of systolic and diastolic cardiac function in hypertension [n = 345; LD 10.1 (+/-standard deviation, SD 2.0 mm), P < 0.001; E/e' 12.4 (x/SD 1.4), P < 0.001], diabetes [n = 65; LD 9.8 (+/-SD 2.2 mm), P < 0.001; E/e' 12.7 (x/SD 1.5), P < 0.001], and IHD [n = 93; LD 9.4 (+/-SD 2.5 mm), P < 0.001; E/e' 13.0 (x/SD 1.5), P < 0.001] compared with controls [n = 533; LD 11.4 (+/-SD 2.0 mm); E/e' 9.0 (x/SD 1.3)]. This pattern remained significant after adjusting for age, sex, body mass index, heart rate, and the results of conventional echocardiography. CONCLUSION: In the general population, persons with hypertension, diabetes, or IHD have impaired cardiac function by TDI independently of the result of conventional echocardiography.