Grace Lin

Right heart dysfunction in heart failure with preserved ejection fraction

AIM Right heart function is not well characterized in patients with heart failure and preserved ejection fraction (HFpEF). The goal of this study was to examine the haemodynamic, clinical, and prognostic correlates of right ventricular dysfunction (RVD) in HFpEF. METHODS AND RESULTS Heart failure and preserved ejection fraction patients (n = 96) and controls (n = 46) underwent right heart catheterization, echocardiographic assessment, and follow-up. Right and left heart filling pressures, pulmonary artery (PA) pressures, and right-sided chamber dimensions were higher in HFpEF compared with controls, while left ventricular size and EF were similar. Right ventricular dysfunction (defined by RV fractional area change, FAC <35%) was present in 33% of HFpEF patients and was associated with more severe symptoms and greater comorbidity burden. Right ventricular function was impaired in HFpEF compared with controls using both load-dependent (FAC: 40 ± 10 vs. 53 ± 7%, P < 0.0001) and load-independent indices (FAC adjusted to PA pressure, P = 0.003), with enhanced afterload-sensitivity compared with controls (steeper FAC vs. PA pressure relationship). In addition to haemodynamic load, RVD in HFpEF was associated with male sex, atrial fibrillation, coronary disease, and greater ventricular interdependence. Over a median follow-up of 529 days (IQR: 143-1066), 31% of HFpEF patients died. In Cox analysis, RVD was the strongest predictor of death (HR: 2.4, 95% CI: 1.6-2.6; P < 0.0001). CONCLUSION Right heart dysfunction is common in HFpEF and is caused by both RV contractile impairment and afterload mismatch from pulmonary hypertension. Right ventricular dysfunction in HFpEF develops with increasing PA pressures, atrial fibrillation, male sex, and left ventricular dysfunction, and may represent a novel therapeutic target.

Magnetic resonance elastography predicts advanced fibrosis in patients with nonalcoholic fatty liver disease: A prospective study

Retrospective studies have shown that two‐dimensional magnetic resonance elastography (2D‐MRE), a novel MR method for assessment of liver stiffness, correlates with advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Prospective data on diagnostic accuracy of 2D‐MRE in the detection of advanced fibrosis in NAFLD are needed. The aim of this study is to prospectively assess the diagnostic accuracy of 2D‐MRE, a noninvasive imaging biomarker, in predicting advanced fibrosis (stage 3 or 4) in well‐characterized patients with biopsy‐proven NAFLD. This is a cross‐sectional analysis of a prospective study including 117 consecutive patients (56% women) with biopsy‐proven NAFLD who underwent a standardized research visit: history, exam, liver biopsy assessment (using the nonalcoholic steatohepatitis Clinical Research Network histological scoring system), and 2D‐MRE from 2011 to 2013. The radiologist and pathologist were blinded to clinical and pathology/imaging data, respectively. Receiver operating characteristics (ROCs) were examined to assess the diagnostic test performance of 2D‐MRE in predicting advanced fibrosis. The mean (± standard deviation) of age and body mass index was 50.1 (± 13.4) years and 32.4 (± 5.0) kg/m2, respectively. The median time interval between biopsy and 2D‐MRE was 45 days (interquartile range: 50 days). The number of patients with fibrosis stages 0, 1, 2, 3, and 4 was 43, 39, 13, 12, and 10, respectively. The area under the ROC curve for 2D‐MRE discriminating advanced fibrosis (stage 3‐4) from stage 0‐2 fibrosis was 0.924 (P < 0.0001). A threshold of >3.63 kPa had a sensitivity of 0.86 (95% confidence interval [CI]: 0.65‐0.97), specificity of 0.91 (95% CI: 0.83‐0.96), positive predictive value of 0.68 (95% CI: 0.48‐0.84), and negative predictive value of 0.97 (95% CI: 0.91‐0.99). Conclusions: MRE is accurate in predicting advanced fibrosis and may be utilized for noninvasive diagnosis of advanced fibrosis in patients with NAFLD. (Hepatology 2014;60:1919–1927)

Device complications and inappropriate implantable cardioverter defibrillator shocks in patients with hypertrophic cardiomyopathy

Background: Although the benefit of implantable cardioverter defibrillator (ICD) therapy in patients with hypertrophic cardiomyopathy (HCM) at risk for sudden cardiac arrest is well established, there may be a higher risk for device complications and inappropriate shocks. Objectives: To determine the incidence of inappropriate ICD shocks and device complications in HCM patients and the impact of young age at ICD implant and atrial fibrillation. Methods: HCM patients who underwent ICD implantation between January 1988 and December 2005 were included. The frequency of device complications, including pneumothorax, pericardial effusion, haematoma, lead revisions, infection and rate of inappropriate shocks, was determined. ICD shocks were characterised as inappropriate if triggered by sinus tachycardia, atrial fibrillation or device malfunction. Results: A total of 181 patients were included (mean age 44 (SD 17) years; 62% males). During a mean follow-up of 59 (42) months (4.92 years; 830.75 patient-years), 65 patients (36%) had a total of 88 device complications, including 42 (23%) patients with inappropriate shocks. The rate of inappropriate shocks was 5.3% per year (vs 4% risk of appropriate shocks), and the likelihood of inappropriate ICD shocks per 100 patient-years was 5.1. Younger age and atrial fibrillation were associated with an increased risk of inappropriate ICD discharges. Conclusions: The rate of inappropriate ICD shocks and frequency of device complications in HCM patients are not insignificant and are most common in younger patients and those with atrial fibrillation. Inappropriate ICD shocks are the most common device complication and should be accounted for when counselling high-risk HCM patients for ICD implantation.

Left Atrial Remodeling and Function in Advanced Heart Failure With Preserved or Reduced Ejection Fraction

Background—Left atrial (LA) structure and function are altered in most heart failure (HF) patients, but there may be fundamental differences in LA properties between HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). Methods and Results—One hundred ninety-eight HF patients (51% HFpEF, New York Heart Association 3.1±0.7) and 40 HF-free controls underwent catheterization, echocardiography, and follow-up. Compared with controls, HF patients had larger and more dysfunctional left atria. At identical mean LA pressure (20 versus 20 mm Hg; P=0.9), HFrEF patients had larger LA volumes (LA volume index 50 versus 41 mL/m2; P<0.001), whereas HFpEF patients had higher LA peak pressures, lower LA minimal pressures, higher LA stiffness (0.79 versus 0.48 mm Hg/mL; P<0.001), greater LA pulsatility (19 versus 13 mm Hg; P<0.001), and higher wall stress variations. Despite smaller LA volumes, better function, and less mitral regurgitation, HFpEF patients had more atrial fibrillation (42 versus 26%; P=0.02). LA dysfunction was associated with increased pulmonary vascular resistance and right ventricular dysfunction in both HF phenotypes. After a median follow-up of 350 days, 31 HFpEF and 28 HFrEF patients died. LA function (total LA EF) was associated with lower mortality in HFpEF (hazard ratio 0.43; 95% confidence interval, 0.2–0.9; P<0.05), but not in HFrEF. Conclusions—HFrEF is characterized by greater eccentric LA remodeling, whereas HFpEF by increased LA stiffness, which might contribute to greater atrial fibrillation burden. LA function is associated with pulmonary vascular disease and right HF in both HF phenotypes, but is associated with outcome more closely in HFpEF, supporting efforts to improve LA function in this cohort.

Dyssynchrony Indices To Predict Response to Cardiac Resynchronization Therapy A Comprehensive Prospective Single-Center Study

Background—Whether mechanical dyssynchrony indices predict reverse remodeling (RR) or clinical response to cardiac resynchronization therapy (CRT) remains controversial. This prospective study evaluated whether echocardiographic dyssynchrony indices predict RR or clinical response after CRT. Methods and Results—Of 184 patients with heart failure with anticipated CRT who were prospectively enrolled, 131 with wide QRS and left ventricular ejection fraction <35% had 6-month follow-up after CRT implantation. Fourteen dyssynchrony indices (feasibility) by M-mode (94%), tissue velocity (96%), tissue Doppler strain (92%), 2D speckle strain (65% to 86%), 3D echocardiography (79%), and timing intervals (98%) were evaluated. RR (end-systolic volume reduction ≥15%) occurred in 55% and more frequently in patients without (71%) than in patients with (42%) ischemic cardiomyopathy (P=0.002). Overall, only M-mode, tissue Doppler strain, and total isovolumic time had a receiver operating characteristic area under the curve (AUC) greater than the line of no information, but none of these were strongly predictive of RR (AUC, 0.63 to 0.71). In nonischemic cardiomyopathy, no dyssynchrony index predicted RR. In ischemic cardiomyopathy, M-mode (AUC, 0.67), tissue Doppler strain (AUC, 0.79), and isovolumic time (AUC, 0.76) -derived indices predicted RR (P<0.05 for all), although the incremental value was modest. No indices predicted clinical response assessed by Minnesota Living with Heart Failure Questionnaire, 6-minute walk distance, and peak oxygen consumption. Conclusions—These findings are consistent with the Predictors of Response to CRT study and do not support use of these dyssynchrony indices to guide use of CRT.

Implantable Cardioverter Defibrillators in Patients with Cardiac Amyloidosis

Cardiac amyloidosis (CA) is associated with increased risk of sudden cardiac arrest. Although ICD therapy improves survival in patients with cardiomyopathy due to other etiologies, the benefit of ICD therapy in patients with CA is unclear in large part due to limited data on the precise mechanism of sudden cardiac arrest and selection of patients with cardiac amyloidosis for ICD therapy.

Regression of Paravalvular Aortic Regurgitation and Remodeling of Self-Expanding Transcatheter Aortic Valve: An Observation From the CoreValve U.S. Pivotal Trial

OBJECTIVES The aim of this study was to describe the natural history and clinical importance of paravalvular aortic regurgitation (PVAR) after CoreValve transcatheter aortic valve replacement (TAVR) and to relate these findings to the structural and hemodynamic changes documented by serial echocardiographic analysis. BACKGROUND PVAR after TAVR with the self-expanding CoreValve bioprosthesis has been shown to regress over time, but the time course and the mechanism of PVAR regression has not been completely characterized. METHODS Patients with severe aortic stenosis who underwent CoreValve TAVR and followed up to 1 year in the multicenter CoreValve U.S. Pivotal Trial (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement) were studied. Serial echocardiography studies were analyzed by an echocardiographic core laboratory. Annular sizing ratio was calculated from computed tomography measurements. Paired, as well as total, data were compared. RESULTS The CoreValve was implanted in 634 patients with a mean age of 82.7 ± 8.4 years. After a marked improvement noted at discharge, aortic valve velocity, mean gradient, and effective orifice area further improved significantly at 1 month (2.08 ± 0.45 m/s vs. 1.99 ± 0.46 m/s, p < 0.0001, 9.7 ± 4.4 mm Hg vs. 8.9 ± 4.6 mm Hg, p < 0.0001, and 1.78 ± 0.51 cm(2) vs. 1.85 ± 0.58 cm(2), p = 0.03, respectively). The improvement was sustained through 1 year. PVAR was moderate or severe in 9.9%, and of 36 patients with moderate PVAR at discharge and paired data, 30 (83%) improved at least 1 grade of regurgitation at 1 year. Annular sizing ratio was significantly associated with the degree of PVAR. CONCLUSIONS There was further improvement in aortic prosthetic valve hemodynamics and regression of PVAR up to 1 year compared with discharge after TAVR with CoreValve. These changes are possibly due to remodeling and outward expansion of the self-expandable CoreValve with nitinol frame. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement [Medtronic CoreValve U.S. Pivotal Trial]; NCT01240902).

Renal function and mortality following cardiac resynchronization therapy.

AIMS Cardiac resynchronization therapy (CRT) improves outcomes in heart failure, yet selection of patients likely to have survival benefit is problematic. Chronic kidney disease (CKD) is an important determinant of mortality in patients with congestive heart failure therefore we sought to determine the impact of CKD on mortality benefit after CRT. METHODS AND RESULTS All CRT device implantations in patients not on dialysis at Mayo Clinic between January 1999 and December 2005 were included. Of 482 patients, 342 (71%) had CKD (defined as a glomerular filtration rate (GFR) of ≤60 mL/min/1.73 m(2)) at the time of device implantation. Patients with CKD were older (71 ± 10 vs. 63 ± 14 years, P < 0.01) than patients without CKD, and more often anaemic (12.70 ± 1.73 vs. 13.24 mg/L, P < 0.01), with similar ejection fraction (22 ± 8 vs. 23 ± 8%, P = 0.32). Survival was superior in patients with normal or mild renal dysfunction compared with patients with CKD (72 vs. 57% at 3 years, P < 0.01). After multivariate analysis, CKD remained a significant predictor of poor survival following CRT. CONCLUSION Chronic kidney disease is common in patients undergoing CRT and associated with a higher mortality and should be considered when evaluating patients for CRT.

Dyssynchrony Indices To Predict Response to Cardiac Resynchronization Therapy

Background—Whether mechanical dyssynchrony indices predict reverse remodeling (RR) or clinical response to cardiac resynchronization therapy (CRT) remains controversial. This prospective study evaluated whether echocardiographic dyssynchrony indices predict RR or clinical response after CRT. Methods and Results—Of 184 patients with heart failure with anticipated CRT who were prospectively enrolled, 131 with wide QRS and left ventricular ejection fraction <35% had 6-month follow-up after CRT implantation. Fourteen dyssynchrony indices (feasibility) by M-mode (94%), tissue velocity (96%), tissue Doppler strain (92%), 2D speckle strain (65% to 86%), 3D echocardiography (79%), and timing intervals (98%) were evaluated. RR (end-systolic volume reduction ≥15%) occurred in 55% and more frequently in patients without (71%) than in patients with (42%) ischemic cardiomyopathy (P=0.002). Overall, only M-mode, tissue Doppler strain, and total isovolumic time had a receiver operating characteristic area under the curve (AUC) greater than the line of no information, but none of these were strongly predictive of RR (AUC, 0.63 to 0.71). In nonischemic cardiomyopathy, no dyssynchrony index predicted RR. In ischemic cardiomyopathy, M-mode (AUC, 0.67), tissue Doppler strain (AUC, 0.79), and isovolumic time (AUC, 0.76) -derived indices predicted RR (P<0.05 for all), although the incremental value was modest. No indices predicted clinical response assessed by Minnesota Living with Heart Failure Questionnaire, 6-minute walk distance, and peak oxygen consumption. Conclusions—These findings are consistent with the Predictors of Response to CRT study and do not support use of these dyssynchrony indices to guide use of CRT.

Effect of cardiac resynchronisation therapy on occurrence of ventricular arrhythmia in patients with implantable cardioverter defibrillators undergoing upgrade to cardiac resynchronisation therapy devices

Background: Cardiac resynchronisation therapy (CRT) improves outcomes in selected patients with heart failure and left ventricular dysfunction. One mechanism of benefit is believed to be favourable ventricular remodelling. Whether CRT also decreases the frequency of ventricular arrhythmias and risk of sudden death is unknown. Objective: To determine the effect of CRT on frequency of ventricular arrhythmias and appropriate ICD therapies. Design: Retrospective cohort study. Setting: Single-centre, tertiary care facility (Mayo Clinic). Patients: 52 patients (46 male), aged 70 (SD 10) years, who underwent upgrade from an implantable cardioverter defibrillator (ICD) to a CRT-defibrillator were included. Interventions: Upgrade of ICD to CRT-defibrillator. Main Outcome Measures: Frequency of ventricular arrhythmias prior to and following upgrade to CRT device. Results: Ejection fraction increased from 22% (SD 8%) to 27% (SD 11%) following CRT. However, the frequency of non-sustained ventricular arrhythmias, sustained ventricular arrhythmias, and ventricular fibrillation was not significantly changed prior to and following CRT (2.38 (SD 9.78) vs 58.51 (SD 412.73) per patient per month, p = 0.66; 0.07 (SD 0.17) vs 0.16 (SD 0.52), p = 0.70; 0.05 (SD 0.12) vs 0.25 (SD 1.40), p = 0.12). Conclusions: CRT is not associated with a decrease in the frequency of ventricular arrhythmia or appropriate device therapy. Thus, use of CRT alone is not beneficial in decreasing the frequency of ventricular arrhythmias or the risk of appropriate ICD therapies.