Martin G. Keane

Comparison of transcatheter and surgical aortic valve replacement in severe aortic stenosis: A longitudinal study of echocardiography parameters in cohort a of the PARTNER trial (Placement of aortic transcatheter valves).

OBJECTIVESnThis study sought to compare echocardiographic findings in patients with critical aortic stenosis following surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR).nnnBACKGROUNDnThe PARTNER (Placement of Aortic Transcatheter Valves) trial randomized patients 1:1 to SAVR or TAVR.nnnMETHODSnEchocardiograms were obtained at baseline, discharge, 30 days, 6 months, 1 year, and 2 years after the procedure and analyzed in a core laboratory. For the analysis of post-implantation variables, the first interpretable study (≤6 months) was used.nnnRESULTSnBoth groups showed a decrease in aortic valve gradients and increase in effective orifice area (EOA) (p < 0.0001), which remained stable over 2 years. Compared with SAVR, TAVR resulted in larger indexed EOA (p = 0.038), less prosthesis-patient mismatch (p = 0.019), and more total and paravalvular aortic regurgitation (p < 0.0001). Baseline echocardiographic univariate predictors of death were lower peak transaortic gradient in TAVR patients, and low left ventricular diastolic volume, low stroke volume, and greater severity of mitral regurgitation in SAVR patients. Post-implantation echocardiographic univariate predictors of death were: larger left ventricular diastolic volume, left ventricular systolic volume and EOA, decreased ejection fraction, and greater aortic regurgitation in TAVR patients; and smaller left ventricular systolic and diastolic volumes, low stroke volume, smaller EOA, and prosthesis-patient mismatch in SAVR patients.nnnCONCLUSIONSnPatients randomized to either SAVR or TAVR experience enduring, significant reductions in transaortic gradients and increase in EOA. Compared with SAVR, TAVR patients had higher indexed EOA, lower prosthesis-patient mismatch, and more aortic regurgitation. Univariate predictors of death for the TAVR and SAVR groups differed and might allow future refinement in patient selection. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

Evidence of Atrial Functional Mitral Regurgitation Due to Atrial Fibrillation : Reversal With Arrhythmia Control

OBJECTIVESnThe purpose of this study was to determine whether atrial fibrillation (AF) might cause significant mitral regurgitation (MR), and to see whether this MR improves with restoration of sinus rhythm.nnnBACKGROUNDnMR can be classified by leaflet pathology (organic/primary and functional/secondary) and by leaflet motion (normal, excessive, restrictive). The existence of secondary, normal leaflet motion MR remains controversial.nnnMETHODSnWe performed a retrospective cohort study. Patients undergoing first AF ablation at our institution (n = 828) were screened. Included patients had echocardiograms at the time of ablation and at 1-year clinical follow-up. The MR cohort (n = 53) had at least moderate MR. A reference cohort (n = 53) was randomly selected from those patients (n = 660) with mild or less MR. Baseline echocardiographic and clinical characteristics were compared, and the effect of restoration of sinus rhythm was assessed by follow-up echocardiograms.nnnRESULTSnMR patients were older than controls and more often had persistent AF (62% vs. 23%, p < 0.0001). MR patients had larger left atria (volume index: 32 cm(3)/m(2) vs. 26 cm(3)/m(2), p = 0.008) and annular size (3.49 cm vs. 3.23 cm, p = 0.001), but similar left ventricular size and ejection fraction. Annular size, age and persistent AF were independently associated with MR. On follow-up echocardiogram, patients in continuous sinus rhythm had greater reductions in left atrial size and annular dimension, and lower rates of significant MR (24% vs. 82%, p = 0.005) compared with those in whom sinus rhythm was not restored.nnnCONCLUSIONSnAF can result in atrial functional MR that improves if sinus rhythm is restored.

Sodium excretion and the risk of cardiovascular disease in patients with chronic kidney disease

IMPORTANCEnPatients with chronic kidney disease (CKD) are at an increased risk of cardiovascular disease (CVD) compared with the general population. Prior studies have produced contradictory results on the association of dietary sodium intake with risk of CVD, and this relationship has not been investigated in patients with CKD.nnnOBJECTIVEnTo evaluate the association between urinary sodium excretion and clinical CVD events among patients with CKD.nnnDESIGN, SETTING, AND PARTICIPANTSnA prospective cohort study of patients with CKD from 7 locations in the United States enrolled in the Chronic Renal Insufficiency Cohort Study and followed up from May 2003 to March 2013.nnnEXPOSURESnThe cumulative mean of urinary sodium excretion from three 24-hour urinary measurements and calibrated to sex-specific mean 24-hour urinary creatinine excretion.nnnMAIN OUTCOMES AND MEASURESnA composite of CVD events defined as congestive heart failure, stroke, or myocardial infarction. Events were reported every 6 months and confirmed by medical record adjudication.nnnRESULTSnAmong 3757 participants (mean age, 58 years; 45% women), 804 composite CVD events (575 heart failure, 305 myocardial infarction, and 148 stroke) occurred during a median 6.8 years of follow-up. From lowest (<2894 mg/24 hours) to highest (≥4548 mg/24 hours) quartile of calibrated sodium excretion, 174, 159, 198, and 273 composite CVD events occurred, and the cumulative incidence was 18.4%, 16.5%, 20.6%, and 29.8% at median follow-up. In addition, the cumulative incidence of CVD events in the highest quartile of calibrated sodium excretion compared with the lowest was 23.2% vs 13.3% for heart failure, 10.9% vs 7.8% for myocardial infarction, and 6.4% vs 2.7% for stroke at median follow-up. Hazard ratios of the highest quartile compared with the lowest quartile were 1.36 (95% CI, 1.09-1.70; Pu2009=u2009.007) for composite CVD events, 1.34 (95% CI, 1.03-1.74; Pu2009=u2009.03) for heart failure, and 1.81 (95% CI, 1.08-3.02; Pu2009=u2009.02) for stroke after multivariable adjustment. Restricted cubic spline analyses of the association between sodium excretion and composite CVD provided no evidence of a nonlinear association (Pu2009=u2009.11) and indicated a significant linear association (Pu2009<u2009.001).nnnCONCLUSIONS AND RELEVANCEnAmong patients with CKD, higher urinary sodium excretion was associated with increased risk of CVD.

Association of cardiac troponin T with left ventricular structure and function in CKD

BACKGROUNDnSerum cardiac troponin T (cTnT) is associated with increased risk of heart failure and cardiovascular death in several population settings. We evaluated associations of cTnT levels with cardiac structural and functional abnormalities in a cohort of patients with chronic kidney disease (CKD) without heart failure.nnnSTUDY DESIGNnCross-sectional.nnnSETTING & PARTICIPANTSnChronic Renal Insufficiency Cohort (CRIC; N=3,243).nnnPREDICTORnThe primary predictor was cTnT level. Secondary predictors included demographic and clinical characteristics, hemoglobin level, high-sensitivity C-reactive protein level, and estimated glomerular filtration rate using cystatin C.nnnOUTCOMESnEchocardiography was used to determine left ventricular (LV) mass and LV systolic and diastolic function.nnnMEASUREMENTSnCirculating cTnT was measured in stored sera using the highly sensitive assay. Logistic and linear regression models were used to examine associations of cTnT level with each echocardiographic outcome.nnnRESULTSncTnT was detectable in 2,735 (84%) persons; median level was 13.3 (IQR, 7.7-23.8) pg/mL. Compared with undetectable cTnT (<3.0 pg/mL), the highest quartile (23.9-738.7 pg/mL) was approximately 2 times as likely to have LV hypertrophy (OR, 2.43; 95% CI, 1.44-4.09) in the fully adjusted model. cTnT level had a more modest association with LV systolic dysfunction; as a log-linear variable, a significant association was present in the fully adjusted model (OR of 1.4 [95% CI, 1.2-1.7] per 1-log unit; P < 0.001). There was no significant independent association between cTnT level and LV diastolic dysfunction. When evaluated as a screening test, cTnT level functioned only modestly for LV hypertrophy and concentric hypertrophy detection (area under the curve, 0.64 for both), with weaker areas under the curve for the other outcomes.nnnLIMITATIONSnThe presence of coronary artery disease was not formally assessed using either noninvasive or angiographic techniques in this study.nnnCONCLUSIONSnIn this large CKD cohort without heart failure, detectable cTnT had a strong association with LV hypertrophy, a more modest association with LV systolic dysfunction, and no association with diastolic dysfunction. These findings indicate that circulating cTnT levels in patients with CKD are predominantly an indicator of pathologic LV hypertrophy.

Association of N-terminal pro-B-type natriuretic peptide with left ventricular structure and function in chronic kidney disease (from the Chronic Renal Insufficiency Cohort [CRIC]).

We evaluated the cross-sectional associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with cardiac structural and functional abnormalities in a cohort of patients with chronic kidney disease without clinical heart failure, the Chronic Renal Insufficiency Cohort (n = 3,232). The associations of NT-proBNP with echocardiographically determined left ventricular (LV) mass and LV systolic and diastolic function were evaluated using multivariate logistic and linear regression models. Reclassification of participants predicted risk of LV hypertrophy (LVH), systolic and diastolic dysfunction was performed using a category-free net reclassification improvement index that compared a clinical model with and without NT-proBNP. The median NT-proBNP was 126.6 pg/ml (interquartile range 55.5 to 303.7). The greatest quartile of NT-proBNP was associated with a nearly threefold odds of LVH (odds ratio 2.7, 95% confidence interval [CI] 1.8 to 4.0) and LV systolic dysfunction (odds ratio 2.7, 95% CI 1.7 to 4.5) and a twofold odds of diastolic dysfunction (odds ratio 2.0, 95% CI 1.3 to 2.9) in the fully adjusted models. When evaluated alone as a screening test, NT-proBNP functioned modestly for the detection of LVH (area under the curve 0.66) and LV systolic dysfunction (area under the curve 0.62) and poorly for the detection of diastolic dysfunction (area under the curve 0.51). However, when added to the clinical model, NT-proBNP significantly reclassified participants likelihood of having LVH (net reclassification improvement 0.14, 95% CI 0.13-0.15; p <0.001) and LV systolic dysfunction (net reclassification improvement 0.28, 95% CI 0.27 to 0.30; p <0.001) but not diastolic dysfunction (net reclassification improvement 0.10, 95% CI 0.10 to 0.11; p = 0.07). In conclusion, in this large chronic kidney disease cohort without heart failure, NT-proBNP had strong associations with prevalent LVH and LV systolic dysfunction.

Hemodynamic Outcomes of Transcatheter Aortic Valve Replacement and Medical Management in Severe, Inoperable Aortic Stenosis: A Longitudinal Echocardiographic Study of Cohort B of the PARTNER Trial

BACKGROUNDnInoperable aortic stenosis may be treated with either transcatheter aortic valve replacement (TAVR) or medical management (MM) with or without balloon aortic valvuloplasty (BAV). The aim of this study was to compare the long-term echocardiographic findings among TAVR, MM, and BAV in patients with severe, inoperable aortic stenosis.nnnMETHODSnA total of 358 inoperable patients in the Placement of Aortic Transcatheter Valves trial were randomized to MM or TAVR. Echocardiograms obtained at baseline, 30 days, and 1, 2, and 3 years were analyzed by a central core laboratory.nnnRESULTSnAt baseline, TAVR and MM were similar, with more frequent Society of Thoracic Surgeons score > 10 (51.7% vs 65.0%, P = .03) and larger end-systolic volumes (54.5 ± 29.3 vs 69.1 ± 48.0 mL, P = .03) in MM. By 30 days after TAVR, mean aortic valve gradient had decreased (from 43.8 ± 14.7 to 10.0 ± 4.3 mm Hg, P < .001), ejection fraction had increased (from 53.2 ± 12.4% to 56.7 ± 10.0%, P < .001), and left ventricular (LV) mass index had decreased (from 144.7 ± 36.1 to 140.0 ± 37.9 gm/m(2), P < .05). After 1 year, aortic valve gradients and area were unchanged, while LV mass index had decreased by another 16 gm/m(2) (to 124 gm/m(2)). By 30 days after BAV, mean aortic valve gradient had decreased from 43.4 ± 15.0 to 31.9 ± 11.1 mm Hg, while ejection fraction and LV mass index were unchanged; gradient reverted to baseline at 1 year. No changes in gradients or mass were seen in MM patients.nnnCONCLUSIONSnTAVR results in immediate and sustained relief in pressure overload and improved LV systolic function, with continued regression of hypertrophy over 3 years. Poor clinical results with BAV are explained by the modest and transient reductions in pressure overload with BAV, which were not accompanied by improved LV function or remodeling. TAVR is the preferred treatment in eligible inoperable patients (ClinicalTrials.gov identifier NCT00530894).

Detailed examination of fenfluramine-phentermine users with valve abnormalities identified in Fargo, North Dakota

Although several studies have reported on valve abnormalities among users of fenfluramine or dexfenfluramine, detailed information on these subjects has not been provided, limiting the ability to understand who may be at risk for valve abnormalities and to generate hypotheses about the etiology and pathogenesis of these abnormalities. This study was a detailed medical record review of 18 previously reported users of fenfluramine and phentermine, all with valve abnormalities on echocardiogram and 2 with surgical pathology. Both clinical characteristics and medication use were recorded by trained abstracters using a standardized data collection form. Two subjects (11%) had other possible etiologies of valve disease: a history of rheumatic fever and prescribed ergotamine. Three subjects (17%) had a history of migraine headaches and 4 (22%) had murmurs noted before using fenfluramine. Use of medications that may affect serotonin receptors was common: ergotamine (1 subject, 5%), selective serotonin reuptake inhibitors (6, 33%), sumatriptan (2, 11%), and mirtazapine (1, 5%). Prior medication and nonmedication allergies were recorded in 6 (33%) and 3 (17%) subjects, respectively. All subjects had symptoms possibly due to fenfluramine or phentermine side effects. This study raises the hypotheses that valvular heart disease among fenfluramine users may be less common than previously estimated, that serotonin excess may play a role in valve pathology, and that a patients response to anorexigens and other medications may serve as a marker for increased risk. Further study is needed to test these hypotheses.

Association between Inflammation and Cardiac Geometry in Chronic Kidney Disease: Findings from the CRIC Study

Background Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function. Methods Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted at a centralized core laboratory. Results LVH, systolic dysfunction and diastolic dysfunction were present in 52.3%, 11.8% and 76.3% of the study subjects, respectively. In logistic regression analysis adjusted for age, sex, race/ethnicity, diabetic status, current smoking status, systolic blood pressure, urinary albumin- creatinine ratio and estimated glomerular filtration rate, hs-CRP (OR 1.26 [95% CI 1.16, 1.37], p<0.001), IL-1RA (1.23 [1.13, 1.34], p<0.0001), IL-6 (1.25 [1.14, 1.36], p<0.001) and TNF-α (1.14 [1.04, 1.25], p = 0.004) were associated with LVH. The odds for systolic dysfunction were greater for subjects with elevated levels of hs-CRP (1.32 [1.18, 1.48], p<0.001) and IL-6 (1.34 [1.21, 1.49], p<0.001). Only hs-CRP was associated with diastolic dysfunction (1.14 [1.04, 1.26], p = 0.005). Conclusion In patients with CKD, elevated plasma levels of hs-CRP and IL-6 are associated with LVH and systolic dysfunction.

Interleukin-6 Is a Risk Factor for Atrial Fibrillation in Chronic Kidney Disease: Findings from the CRIC Study

Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with chronic kidney disease (CKD). In this study, we examined the association between inflammation and AF in 3,762 adults with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. AF was determined at baseline by self-report and electrocardiogram (ECG). Plasma concentrations of interleukin(IL)-1, IL-1 Receptor antagonist, IL-6, tumor necrosis factor (TNF)-α, transforming growth factor-β, high sensitivity C-Reactive protein, and fibrinogen, measured at baseline. At baseline, 642 subjects had history of AF, but only 44 had AF in ECG recording. During a mean follow-up of 3.7 years, 108 subjects developed new-onset AF. There was no significant association between inflammatory biomarkers and past history of AF. After adjustment for demographic characteristics, comorbid conditions, laboratory values, echocardiographic variables, and medication use, plasma IL-6 level was significantly associated with presence of AF at baseline (Odds ratio [OR], 1.61; 95% confidence interval [CI], 1.21 to 2.14; P = 0.001) and new-onset AF (OR, 1.25; 95% CI, 1.02 to 1.53; P = 0.03). To summarize, plasma IL-6 level is an independent and consistent predictor of AF in patients with CKD.

Serum Aldosterone and Death, End-Stage Renal Disease, and Cardiovascular Events in Blacks and Whites: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Prior studies have demonstrated that elevated aldosterone concentrations are an independent risk factor for death in patients with cardiovascular disease. Limited studies, however, have evaluated systematically the association between serum aldosterone and adverse events in the setting of chronic kidney disease. We investigated the association between serum aldosterone and death and end-stage renal disease in 3866 participants from the Chronic Renal Insufficiency Cohort. We also evaluated the association between aldosterone and incident congestive heart failure and atherosclerotic events in participants without baseline cardiovascular disease. Cox proportional hazards models were used to evaluate independent associations between elevated aldosterone concentrations and each outcome. Interactions were hypothesized and explored between aldosterone and sex, race, and the use of loop diuretics and renin–angiotensin–aldosterone system inhibitors. During a median follow-up period of 5.4 years, 587 participants died, 743 developed end-stage renal disease, 187 developed congestive heart failure, and 177 experienced an atherosclerotic event. Aldosterone concentrations (per SD of the log-transformed aldosterone) were not an independent risk factor for death (adjusted hazard ratio, 1.00; 95% confidence interval, 0.93–1.12), end-stage renal disease (adjusted hazard ratio, 1.07; 95% confidence interval, 0.99–1.17), or atherosclerotic events (adjusted hazard ratio, 1.04; 95% confidence interval, 0.85–1.18). Aldosterone was associated with congestive heart failure (adjusted hazard ratio, 1.21; 95% confidence interval, 1.02–1.35). Among participants with chronic kidney disease, higher aldosterone concentrations were independently associated with the development of congestive heart failure but not for death, end-stage renal disease, or atherosclerotic events. Further studies should evaluate whether mineralocorticoid receptor antagonists may reduce adverse events in individuals with chronic kidney disease because elevated cortisol levels may activate the mineralocorticoid receptor.Prior studies have demonstrated that elevated aldosterone concentrations are an independent risk factor for death in patients with cardiovascular disease. Limited studies, however, have evaluated systematically the association between serum aldosterone and adverse events in the setting of chronic kidney disease. We investigated the association between serum aldosterone and death and end-stage renal disease in 3866 participants from the Chronic Renal Insufficiency Cohort. We also evaluated the association between aldosterone and incident congestive heart failure and atherosclerotic events in participants without baseline cardiovascular disease. Cox proportional hazards models were used to evaluate independent associations between elevated aldosterone concentrations and each outcome. Interactions were hypothesized and explored between aldosterone and sex, race, and the use of loop diuretics and renin–angiotensin–aldosterone system inhibitors. During a median follow-up period of 5.4 years, 587 participants died, 743 developed end-stage renal disease, 187 developed congestive heart failure, and 177 experienced an atherosclerotic event. Aldosterone concentrations (per SD of the log-transformed aldosterone) were not an independent risk factor for death (adjusted hazard ratio, 1.00; 95% confidence interval, 0.93–1.12), end-stage renal disease (adjusted hazard ratio, 1.07; 95% confidence interval, 0.99–1.17), or atherosclerotic events (adjusted hazard ratio, 1.04; 95% confidence interval, 0.85–1.18). Aldosterone was associated with congestive heart failure (adjusted hazard ratio, 1.21; 95% confidence interval, 1.02–1.35). Among participants with chronic kidney disease, higher aldosterone concentrations were independently associated with the development of congestive heart failure but not for death, end-stage renal disease, or atherosclerotic events. Further studies should evaluate whether mineralocorticoid receptor antagonists may reduce adverse events in individuals with chronic kidney disease because elevated cortisol levels may activate the mineralocorticoid receptor.nn# Novelty and Significance {#article-title-42}