Ratio of Transmitral Early Filling Velocity to Early Diastolic Strain Rate Predicts All-Cause Mortality in Heart Failure with Reduced Ejection Fraction.

AIMS: The ratio of early mitral inflow velocity to global diastolic strain rate (E/e'sr) has recently emerged as a novel measure of left ventricular (LV) filling pressure. This new measure has demonstrated to have prognostic value superior to E/e'. This study aimed to investigate the prognostic value of E/e'sr in a large cohort of patients with heart failure with reduced ejection fraction (HFrEF) in relation to all-cause mortality. METHODS: We retrospectively studied 897 HFrEF (mean age 66 ± 12 years, 73% male, 59% ischemic cardiomyopathy) patients who underwent speckle tracking echocardiography where E/e'sr along with novel and conventional echocardiographic parameters were obtained. The primary endpoint was defined as all-cause mortality. RESULTS: During follow-up (median: 40 months IQR: 22-57), 137 (15.3%) patients died. Both E/e'sr and E/e' were significantly associated with mortality (E/e'sr: HR 1.03 95%CI [1.02-1.04], p<0.001, per 0.10m increase) and (E/e': HR 1.04 95%CI [1.02-1.06], p = 0.001, per 1unit increase). E/e'sr remained an independent predictor in a multivariable model after adjusting for age, gender, mean arterial pressure, heart rate, BMI, total cholesterol, diabetes mellitus, ischemic cardiomyopathy, LVEF, LVIDd, LVMI, LAVI, TAPSE and LV-GLS (HR 1.02 95%CI [1.01-1.03], p = 0.007) whereas E/e' did not (HR 1.01 95%CI [0.98-1.04], p = 0.57). Furthermore, E/e'sr provided incremental prognostic information beyond a model including known risk factors: age, gender, total cholesterol, mean arterial pressure, heart rate, BMI, smoking status and E/e' (Harrell's C-statistics: 0.72 (0.68-0.77) vs 0.70 (0.66-0.75), p = 0.047). CONCLUSIONS: In HFrEF patients, E/e'sr provides independent and incremental prognostic information regarding all-cause mortality superior to E/e'.

Preoperative Echocardiography for Patients With Hip Fractures Undergoing Surgery: A Retrospective Cohort Study Using a Nationwide Database.

BACKGROUND: The effect of preoperative transthoracic echocardiography on the clinical outcomes of patients with hip fractures undergoing surgical treatment remains controversial. We hypothesized that preoperative echocardiography is associated with reduced postoperative morbidity and improved patient survival after surgical repair of hip fractures. METHODS: Drawing from a nationwide administrative database, patients undergoing hip fracture surgeries between April 1, 2008 and December 31, 2016 were included. We examined the association of preoperative echocardiography with the incidence of in-hospital mortality using propensity score matching. Secondary outcomes included postoperative complications, the incidence of postoperative intensive care unit admissions, and length of hospital stay. For sensitivity analyses, we restricted the overall cohort to include only hip fracture surgeries performed within 2 days from admission. RESULTS: Overall, 34,679 (52.1%) of 66,620 surgical patients underwent preoperative echocardiography screening. The screened patients (mean [SD] age, 84.3 years [7.7 years]; 79.0% female) were propensity score matched to 31,941 nonscreened patients (mean [SD] age, 82.1 years [8.7 years]; 78.2% female). The overall in-hospital mortality, before propensity matching, was 1.8% (1227 patients). Propensity score matching created a matched cohort of 25,205 pairs of patients. There were no in-hospital mortality differences between the 2 groups (screened versus nonscreened: 417 [1.65%] vs 439 [1.74%]; odds ratio, 0.95; 95% confidence interval, 0.83-1.09; P = .45). Preoperative echocardiography was not associated with reduced postoperative complications and intensive care unit admissions. In sensitivity analysis, we identified 25,637 patients from the overall cohort (38.5%) with hip fracture surgeries performed within 2 days of admission. There were no in-hospital mortality differences between the 2 groups (screened versus nonscreened: 1.67% vs 1.80%; odds ratio, 0.93; 95% confidence interval, 0.72-1.18; P = .53). Findings were also consistent with other sensitivity analyses and subgroup analyses. CONCLUSIONS: This large, retrospective, nationwide cohort study demonstrated that preoperative echocardiography was not associated with reduced in-hospital mortality or postoperative complications.

Evolution of Echocardiographic Measures of Cardiac Disease From CKD to ESRD and Risk of All-Cause Mortality: Findings From the CRIC Study.

RATIONALE & OBJECTIVE: Abnormal cardiac structure and function are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD) and linked with mortality and heart failure. We examined changes in echocardiographic measures during the transition from CKD to ESRD and their associations with post-ESRD mortality. STUDY DESIGN: Prospective study. SETTING & PARTICIPANTS: We studied 417 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) who had research echocardiograms during CKD and ESRD. PREDICTOR: We measured change in left ventricular mass index, left ventricular ejection fraction (LVEF), diastolic relaxation (normal, mildly abnormal, and moderately/severely abnormal), left ventricular end-systolic (LVESV), end-diastolic (LVEDV) volume, and left atrial volume from CKD to ESRD. OUTCOMES: All-cause mortality after dialysis therapy initiation. ANALYTICAL APPROACH: Cox proportional hazard models were used to test the association of change in each echocardiographic measure with postdialysis mortality. RESULTS: Over a mean of 2.9 years between pre- and postdialysis echocardiograms, there was worsening of mean LVEF (52.5% to 48.6%; P<0.001) and LVESV (18.6 to 20.2mL/m2.7; P<0.001). During this time, there was improvement in left ventricular mass index (60.4 to 58.4g/m2.7; P=0.005) and diastolic relaxation (11.11% to 4.94% with moderately/severely abnormal; P=0.02). Changes in left atrial volume (4.09 to 4.15mL/m2; P=0.08) or LVEDV (38.6 to 38.4mL/m2.7; P=0.8) were not significant. Worsening from CKD to ESRD of LVEF (adjusted HR for every 1% decline in LVEF, 1.03; 95% CI, 1.00-1.06) and LVESV (adjusted HR for every 1mL/m2.7 increase, 1.04; 95% CI, 1.02-1.07) were independently associated with greater risk for postdialysis mortality. LIMITATIONS: Some missing or technically inadequate echocardiograms. CONCLUSIONS: In a longitudinal study of patients with CKD who subsequently initiated dialysis therapy, LVEF and LVESV worsened and were significantly associated with greater risk for postdialysis mortality. There may be opportunities for intervention during this transition period to improve outcomes.

Echocardiographic Determinants of One-Year All-Cause Mortality in Patients With Chronic Heart Failure Complicated by Significant Functional Tricuspid Regurgitation.

BACKGROUND: Right ventricular (RV) dysfunction plays an important role in chronic heart failure (CHF). We evaluated the echocardiographic determinants of 1-year all-cause mortality in CHF patients with clinically relevant functional tricuspid regurgitation (TR). METHODS AND RESULTS: A total of 101 consecutive CHF patients (mean age 74 ± 10 years, 53% male) with moderate or severe functional TR were enrolled. Each patient underwent at least 2 echocardiography examinations in an interval of >6 months. Clinical follow-up was made after a median of 305 (interquartile range 164-365) days after the last echocardiography. The primary end point was all-cause mortality. Forty-two patients (42%) died during follow-up. Baseline right atrial (RA) area, TR volume increase and RV enlargement over time were significantly higher in nonsurvivors than survivors (all P < .05). Compared to baseline levels, systolic pulmonary artery pressure (sPAP) was significantly reduced in nonsurvivors during follow-up echocardiography (54 ± 19 vs 49 ± 21 mm Hg; P = .010), but significantly increased in survivors (48 ± 17 vs 54 ± 17 mm Hg; P = .001). Multivariable survival analysis suggested that baseline RA area ≥27 cm2 (hazard ratio [HR] 2.41, 95% confidence interval [CI] 1.21-4.80; P = .013), follow-up TR proximal isovelocity surface area regurgitant volume increase ≥15 mL (HR 2.27, 95% CI 1.20-4.31; P = .012), RV middle diameter increase ≥10 mm (HR 2.38, 95% CI 1.10-5.11; P = .027), and sPAP reduction ≥10 mm Hg (HR 3.04, 95% CI 1.51-6.13; P = .002) were determinants of 1-year all-cause mortality after the last echocardiography. Patients with 2 or 3 of these determinants were faced with significantly increased 1-year mortality (88% or 100%). CONCLUSIONS: Dynamic RV morphologic and functional changes during serial echocardiography are associated with significantly increased mortality risk in CHF patients with moderate or severe functional TR.

Administration of perflutren contrast agents during transthoracic echocardiography is not associated with a significant increase in acute mortality risk.

BACKGROUND: Despite the 2008 revision of a previously issued black box warning of the US Food and Drug Administration against the use of perflutren ultrasound contrast agents, the warning still reports fatalities having occurred following their administration. We sought to assess 1-day mortality associated with contrast use across a wide range of clinical settings and co-morbidities. METHODS: We conducted a retrospective study involving 96,705 transthoracic echocardiograms (TTE) in 63,189 adults at our institution between July 2003 and June 2008. A contrast agent was used in 2,518 TTE during this time. The primary outcome was total mortality within 1 day of TTE. RESULTS: Death occurred in 10 patients (0.44%) in the contrast group and in 421 patients (0.69%) in the non-contrast group (p = 0.14). In a multivariate model, use of contrast enhancement was not associated with increased mortality (p = 0.67) after adjustment for age, gender, race, patient location, ejection fraction, and the presence of various co-morbidities. Cause of death analysis did not identify any cases where contrast played a likely role. CONCLUSION: Definity contrast use during TTE was not associated with increased acute mortality risk. Contrast administration during TTE should not be withheld when the additional information obtained could potentially improve patient management.

Preoperative Noninvasive Cardiac Testing in Older Adults with Hip Fracture: A Multi-Site Study.

BACKGROUND/OBJECTIVES: For older adults with acute hip fracture, use of preoperative noninvasive cardiac testing may lead to delays in surgery, thereby contributing to worse outcomes. Our study objective was to evaluate the preoperative use of pharmacologic stress testing and transthoracic echocardiogram (TTE) in older adults hospitalized with hip fracture. DESIGN: Retrospective chart review. SETTING: Seven hospitals (three tertiary, four community) within a large health system. PARTICIPANTS: Patients, aged 65 years and older, hospitalized with hip fracture (n = 1,079; mean age = 84.2 years; 75% female; 82% white; 36% married). MEASUREMENTS: Data were extracted from electronic medical records. The study evaluated associations between patient factors as well as clinical outcomes (time to surgery [TTS], length of stay [LOS], and in-hospital mortality) and the use of preoperative noninvasive cardiac testing (pharmacologic stress tests or TTE). Descriptive statistics were calculated. Cox regression was performed for both TTS and LOS (evaluated as time-dependent variable); logistic regression was used for in-hospital mortality. RESULTS: Although 34.3% (n = 370) had a preoperative TTE, .7% (n = 8) underwent a nuclear stress test and none had a dobutamine stress echocardiogram. Median TTS was 1.1 days (IQR [interquartile range] = .8-1.8 days), median LOS was 5.3 days (IQR = 4.2-7.2 days), and in-hospital mortality was 3% (n = 32). Patients admitted to the medical service had 3.5 times greater odds of undergoing a TTE compared with those on the orthopedic service (P < .001). Community hospitals had almost three times greater odds of preoperative TTE than tertiary centers (P < .001). In multivariable analysis, preoperative TTE was significantly associated with increased TTS (P < .001). No difference in mortality was found between patients with and without a preoperative TTE. CONCLUSION: This study highlights the high rate of TTE in preoperative assessment of older adults with acute hip fracture. Given the association between TTE and longer TTS, further studies must clarify the role of preoperative TTE in this population. J Am Geriatr Soc 68:1690-1697, 2020.

Clinical impact of post procedural mitral regurgitation after transcatheter aortic valve replacement.

BACKGROUND: While the impact of mitral regurgitation (MR) prior to transcatheter aortic valve replacement (TAVR) has been intensively studied, the implications of post-procedural MR on outcome are unknown. We investigated the clinical and physiological impact of significant MR after TAVR. METHODS: Clinical and echocardiographic data of 486 patients who underwent TAVR between March 2009 and December 2014 were evaluated. Clinical endpoints included overall mortality and combined endpoint of mortality, heart failure re-hospitalization and new atrial fibrillation. Echocardiographic parameters were analyzed at baseline, 30-day and 6-month after TAVR. RESULTS: MR severity improved in 25%, worsened in 19% and did not change in 56% of patients 30-days post TAVR (p = 0.3). Post TAVR MR grade ≥ moderate was present in 16.1%. Predictive accuracy of post TAVR MR was low (AUC = 0.63). Median follow-up was 4.3 years (interquartile range, 2.5 to 6.1). Post TAVR MR grade ≥ moderate was associated with increased mortality and combined cardiac events (p = 0.013 and p < 0.001) even when adjusted for all clinical and echo parameters and when analyzed with propensity score matching. In patients with MR ≥ moderate, LV filling pressure and RV hemodynamics worsened 6 months post TAVR, while improving in patients with less significant post procedural MR. CONCLUSION: Post procedural, but not pre-procedural MR grade ≥ moderate was independently associated with mortality and adverse cardiac events after TAVR. Significant MR post TAVR resulted in adverse LV and RV remodeling and poor hemodynamic. Our study strengthens the rational for initiating early treatment to reduce post TAVR MR.

No Obesity Paradox in Pediatric Patients With Dilated Cardiomyopathy.

OBJECTIVES: This study aimed to examine the role of nutrition in pediatric dilated cardiomyopathy (DCM). BACKGROUND: In adults with DCM, malnutrition is associated with mortality, whereas obesity is associated with survival. METHODS: The National Heart, Lung, and Blood Institute-funded Pediatric Cardiomyopathy Registry was used to identify patients with DCM and categorized by anthropometric measurements: malnourished (MN) (body mass index [BMI] <5% for age ≥2 years or weight-for-length <5% for <2 years), obesity (BMI >95% for age ≥2 years or weight-for-length >95% for <2 years), or normal bodyweight (NB). Of 904 patients with DCM, 23.7% (n = 214) were MN, 13.3% (n=120) were obese, and 63.1% (n=570) were NB. RESULTS: Obese patients were older (9.0 vs. 5.7 years for NB; p < 0.001) and more likely to have a family history of DCM (36.1% vs. 23.5% for NB; p = 0.023). MN patients were younger (2.7 years vs. 5.7 years for NB; p < 0.001) and more likely to have heart failure (79.9% vs. 69.7% for NB; p = 0.012), cardiac dimension z-scores >2, and higher ventricular mass compared with NB. In multivariable analysis, MN was associated with increased risk of death (hazard ratio [HR]: 2.06; 95% confidence interval [CI]: 1.66 to 3.65; p < 0.001); whereas obesity was not (HR: 1.49; 95% CI: 0.72 to 3.08). Competing outcomes analysis demonstrated increased risk of mortality for MN compared with NB (p = 0.03), but no difference in transplant rate (p = 0.159). CONCLUSIONS: Malnutrition is associated with increased mortality and other unfavorable echocardiographic and clinical outcomes compared with those of NB. The same effect of obesity on survival was not observed. Further studies are needed investigating the long-term impact of abnormal anthropometric measurements on outcomes in pediatric DCM. (Pediatric Cardiomyopathy Registry; NCT00005391).

Expert Review on the Prognostic Role of Echocardiography after Acute Myocardial Infarction.

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide, placing a major economic and resource burden on public health systems. During hospitalization, all AMI patients should be evaluated with transthoracic echocardiography, a noninvasive, low-cost, and easily available bedside imaging tool that allows the detection of myocardial walls involved in the ischemic process, damage extent, functional consequences, and mechanical complications. Moreover, and more importantly, transthoracic echocardiography can provide information on short- and long-term outcomes after AMI. The purpose of this review is to clarify the role of standard and advanced echocardiographic parameters for an early identification of patients at high risk for developing adverse events and mortality after AMI. Standard echocardiography (in particular left ventricular ejection fraction, wall motion score index, and diastolic measurements including E velocity deceleration time and E/e' ratio) proposes powerful parameters for risk stratification after AMI. Advanced echocardiographic technologies, in particular speckle-tracking-derived longitudinal strain, coronary flow velocity reserve, and myocardial contrast echocardiography (contrast defect index), can provide additional prognostic value beyond standard techniques. Therefore, echocardiography plays a fundamental role in predicting short- and long-term prognosis, and a more accurate risk stratification of patients may be useful to drive therapy and follow-up after AMI. Accordingly, a comprehensive echocardiography-based algorithm would be welcome for an early stratification of cardiovascular risk in patients experiencing AMI.

Right ventriculo-arterial coupling assessed by two-dimensional strain: A new parameter of right ventricular function independently associated with prognosis in chronic heart failure patients.

AIM OF THE STUDY: To evaluate whether right ventriculo-arterial coupling obtained by the estimation of the two-dimensional right ventricular (RV) longitudinal strain and of the pulmonary arterial systolic pressure (PASP) could improve prognostic stratification of chronic heart failure (CHF) outpatients. METHODS: CHF outpatients in a stable clinical condition and in conventional therapy were enrolled. The global RV longitudinal strain (RV-GLS) and the strain of the RV free wall (RV-fwLS) were evaluated. PASP was estimated on the basis of tricuspid regurgitation velocity and the estimated central venous pressure. Both RV-GLS and RV-fwLS were then indexed for PASP. RESULTS: Of the 315 patients evaluated, 69 died during follow-up. Both RV-GLS/PASP and RV-fwLS/PASP were significantly associated with an increased risk of death at univariate (HR: 0.43; 95%CI: 0.34-0.56; p<0.001 and HR: 0.44; 95% CI: 0.34-0.57; p<0.001, respectively) and multivariate analysis (HR: 0.66; 95% CI: 0.49-0.89; p: 0.008 and HR: 0.65; 95% CI: 0.49-0.85; p: 0.002, respectively) after correction for age, NYHA class, mean arterial pressure, left ventricular ejection fraction, natremia, glomerular filtration rate and NT-proBNP. CONCLUSIONS: Indexing RV function, assessed by speckle-tracking analysis, with an estimation of pulmonary systolic arterial pressure provides a parameter of ventricular arterial coupling that is independently associated with an increased risk of mortality.

Impact of right ventricular size and function on survival following transcatheter aortic valve replacement.

BACKGROUND: The impact of pre-procedural RV size and function on outcomes following transcatheter aortic valve replacement (TAVR) is not well established. The aim of this study was to investigate the role of right ventricular size and function on outcomes following TAVR. METHODS AND RESULTS: Between November 2008 and June 2013, 268 consecutive patients (age 80.5±7.9years, aortic valve area 0.79±0.16cm(2)) with symptomatic severe aortic stenosis (AS) undergoing TAVR at Mayo Clinic were included. Transthoracic echocardiographic quantitative and semiquantitative assessment of RV chamber size and systolic function was performed and included tricuspid annular plane systolic excursion (TAPSE), RV systolic excursion velocity (S'), fractional area change (FAC), RV index of myocardial performance (RIMP). The primary endpoint of all-cause mortality after TAVR was measured and observed in 65 patients (median follow up duration: 412days). Univariate analysis identified semiquantitative RV dilatation (p<0.001) and systolic dysfunction (p=0.013), RV basal dimension (p=0.003) and RV outflow proximal dimension (p=0.031) to be of prognostic significance. After multivariate adjustment, patients with semiquantitative RV dilatation (HR 2.61, 95% CI 1.45-4.65, p=0.002) and larger RV basal dimension (HR 1.07, 95% CI per mm 1.02-1.11, p=0.007) had significantly worse survival even after adjusting for age, sex, Society of Thoracic Surgeons (STS) risk score, left ventricular ejection fraction, tricuspid regurgitation, pulmonary artery systolic pressure, and atrial fibrillation. CONCLUSION: RV dilatation is an important determinant of postoperative outcomes in patients undergoing TAVR.

The TRIBECA study: (TRI)fecta (B)ioprosthesis (E)valuation versus (C)arpentier Magna-Ease in (A)ortic position.

OBJECTIVE: To determine whether the Trifecta bioprosthetic aortic valve produces postoperative haemodynamic results comparable with or better than those of the Magna Ease aortic valve bioprosthesis. METHODS: We retrospectively reviewed the medical records of patients who had undergone aortic valve replacement with Trifecta or Magna Ease prostheses at eight European institutions between January 2011 and May 2013, and analysed early postoperative haemodynamic performance by means of echocardiography. RESULTS: A total of 791 patients underwent aortic valve replacement (469 Magna Ease, 322 Trifecta). Haemodynamic variables were evaluated on discharge and during the follow-up (minimum 6 months, maximum 12 months). The mean gradient and the indexed effective orifice area (IEOA) were as follows: 10 mmHg [interquartile range (IQR): 8-13] and 1.10 cm(2)/m(2) (IQR: 0.95-1.27) for Trifecta; 16 mmHg (IQR: 11-22) and 0.96 cm(2)/m(2) (IQR: 0.77-1.13) for Magna Ease (P < 0.001). These significant differences were maintained across all valve sizes. Similar statistically significant differences were found when patients were matched and/or stratified for preoperative characteristics: body-surface area, ejection fraction, mean gradients and valve size. Severe prosthesis-patient mismatch (IEOA: <0.65 cm(2)/m(2)) was detected in 2 patients (0.6%) with Trifecta and 40 patients (8.5%) with Magna Ease (P < 0.001). CONCLUSIONS: The haemodynamic performance of the Trifecta bioprosthesis was superior to that of the Magna Ease valve across all conventional prosthesis sizes, with almost no incidence of severe patient-prosthesis mismatch. The long-term follow-up is needed to determine whether these significant haemodynamic differences will persist, and influence clinical outcomes.

Clinical profile and in-hospital outcome of Caucasian patients with takotsubo syndrome and right ventricular involvement.

AIM: To determine the prevalence, clinical characteristics, in-hospital course and determinants of major adverse events in a cohort of Caucasian patients with Takotsubo syndrome (TTS) and right ventricular involvement (RVi), regardless of left ventricular variant forms. METHODS AND RESULTS: The study population consisted of 424 patients (mean age 69.1±11.5years; female 92.2%) with a diagnosis of TTS divided into two groups according to the presence or absence of RVi. RVi patients (n=57; 13.4%) showed a higher prevalence of comorbidities, especially respiratory diseases (p=0.011), and a higher Charlson comorbidity index (CCI; p=0.006) than non-RVi patients. In-hospital major adverse events (acute heart failure, cardiogenic shock and death) occurred more frequently in RVi patients (p<0.001). Heart rate and CCI, along with the echocardiographic parameters of wall motion score index, E/e' ratio, tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP) were associated with adverse in-hospital outcome. At multivariate analysis, CCI (HR: 1.871; 95% CI: 1.202-2.912; p=0.006), sPAP (HR: 1.059; 95% CI: 1.016-1.104; p=0.007) and TAPSE (HR: 0.728; 95% CI: 0.619-0.855; p<0.001) were independent correlates of the composite outcome in patients with RVi. CONCLUSION: Patients with RVi are characterized by distinct clinical profile and should undergo closely clinical and echocardiographic monitoring. The presence of echocardiographic signs of right ventricular failure along with substantial comorbidities burden identify a cohort at higher risk of in-hospital major adverse cardiovascular events.

Effect of advanced chronic kidney disease in clinical and echocardiographic outcomes of patients treated with MitraClip system.

BACKGROUND: Data regarding the influence of different levels of renal dysfunction on clinical and echocardiographic results of MitraClip therapy are scarce. We aimed to evaluate the impact of baseline advance renal failure in the outcomes of a cohort of patients treated with MitraClip. METHODS AND RESULTS: We analyzed data from a multicenter registry of 173 patients treated with MitraClip between 2009 and 2012. Patients were classified as advanced chronic kidney disease (CKD, creatinine clearance [CrCl] <30 ml/min, group 1, n=20), moderate CKD (CrCl 30-60 ml/min, group 2, n=78) and normal renal function (CrCl >60 ml/min, group 3, n=75). Twenty patients (11.5%) presented advanced CKD. Procedural success was equal in the 3 groups (95.0% group 1, 100% in group 2 and 96.0% in group 3, p=0.180). Post-procedural MR and NYHA class at 1 month (MR ≥ 3+5.0% vs. 0% vs. 4.0% p=0.190 and NYHA>II 40.0% vs. 21.0% vs. 18.3%, p=0.101) and 6 months (MR ≥ 3+0% vs. 13.0% vs. 2.7%, p=0.330; and NYHA class>II 54.5% vs. 26.9% vs. 25.6%, p=0.298) did not differ between groups. However, patients in group 1 experienced higher frequency of the composite end-point of mortality or readmission at 16.2 ± 11.1 months of follow-up (HR 4.8, CI 95% 1.1-21.3). CONCLUSION: Advanced CKD is linked to an excess of cardiac adverse events. This should be judiciously taken into account when selecting patients for MitraClip.

An observational study of the occurrence of serious adverse reactions among patients who receive optison in routine medical practice.

BACKGROUND: Reports of ultrasound contrast agent safety have been derived mainly from retrospective databases rather than from studies specifically designed to assess safety. The purpose of this study was to prospectively determine the safety of Optison (GE Healthcare, Princeton, NJ) in routine medical practice. METHODS: Patients referred for routine rest or stress two-dimensional echocardiography who had indications for contrast were enrolled. Vital signs were obtained at baseline and at intervals up to 1 hour after dosing of Optison. Patients were followed for the development of any serious adverse event (SAE), defined as an event that causes death, is life threatening, requires or prolongs hospitalization, or causes another important event, for 24 hours after Optison administration. RESULTS: A total of 1,039 patients were enrolled, and 76% had 24-hour follow-up. The median age was 60 years (range, 20-97 years), and 62% were men. The mean body mass index was 33 ± 9 kg/m(2). Patient comorbidities included hypertension (73%), hyperlipidemia (64%), smoking (52%), and diabetes (37%). There were significant increases in systolic blood pressure, heart rate, and respiratory rate between the baseline, 5- to 15-min, 30-min, and 60-min time points after the administration of Optison in patients undergoing stress studies but none in those undergoing rest studies. There was a total of six SAEs during the study, which were felt to be related not to Optison but rather to the stress test itself or to the patient's underlying pathology. Although two events were classified as SAEs because of hospitalization, the hospitalizations were appropriate for pathology that would have been missed without Optison use. CONCLUSIONS: In this large, prospective safety study of Optison during routine resting and stress echocardiography, no SAEs related to Optison developed. Optison helped define abnormalities that required appropriate hospitalization for further management.

Prognostic benefit of optimum left ventricular lead position in cardiac resynchronization therapy: follow-up of the TARGET Study Cohort (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy).

OBJECTIVES: This study was conducted to assess the impact of left ventricular (LV) lead position on longer-term survival after cardiac resynchronization therapy (CRT). BACKGROUND: An optimal LV lead position in CRT is associated with improved clinical outcome. A strategy of speckle-tracking echocardiography can be used to guide the implanter to the site of latest activation and away from segments of low strain amplitude (scar). Long-term, prospective survival data according to LV lead position in CRT are limited. METHODS: Data from a follow-up registry of 250 consecutive patients receiving CRT between June 2008 and July 2010 were studied. The study population comprised patients recruited to the derivation group and the subsequent TARGET (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy) randomized, controlled trial. Final LV lead position was described, in relation to the pacing site determined by pre-procedure speckle-tracking echocardiography, as optimal (concordant/adjacent) or suboptimal (remote). All-cause mortality was recorded at follow-up. RESULTS: An optimal LV lead position (n = 202) conferred LV remodeling response superior to that of a suboptimal lead position (change in LV end-systolic volume: -24 ± 15% vs. -12 ± 17% [p < 0.001]; change in ejection fraction: +7 ± 8% vs. +4 ± 7% [p = 0.02]). During long-term follow-up (median: 39 months; range: <1 to 61 months), an optimal LV lead position was associated with improved survival (log-rank p = 0.003). A suboptimal LV lead placement independently predicted all-cause mortality (hazard ratio: 1.8; p = 0.024). CONCLUSIONS: An optimal LV lead position at the site of latest mechanical activation, avoiding low strain amplitude (scar), was associated with superior CRT response and improved survival that persisted during follow-up.

Meta-analysis of adverse cardiovascular events associated with echocardiographic contrast agents.

In October 2007, the Federal Drug Agency issued a black box warning for contrast agents used in patients undergoing echocardiography and restricted their use in patients with acute coronary syndrome, a decompensated heart, and respiratory failure. We performed a systemic review and meta-analysis to study the adverse effects of contrast agents used with respect to myocardial infarction and all-cause mortality. MEDLINE, EMBASE, BIOSIS, and Cochrane databases from inception to October 2009 were searched for studies that reported myocardial infarction and all-cause mortality after the use of contrast agents for echocardiography. A total of 8 studies were included in the present meta-analysis. A random-effect model was used, and between-studies heterogeneity was estimated with I(2). A total of 8 studies reported death as an outcome and only 4 reported myocardial infarction. The incidence of death in the contrast group was 0.34% (726 of 211,162 patients) compared to 0.9% (45,970 of 5,078,666 patients) in the noncontrast group. The pooled odds ratio was 0.57 (95% confidence interval 0.32 to 1.01, p = 0.05). The reported incidence of myocardial infarction in the contrast group was 0.15% (86 of 57,264 patients) compared to 0.2% (92 of 44,503 patients) in the noncontrast group. The pooled odds ratio was 0.85 (95% confidence interval 0.35 to 2.05, p = 0.72). Significant heterogeneity was seen among the studies. In conclusion, the cumulative evidence has suggested that the use of contrast agents for echocardiography is safe and not associated with a greater incidence of myocardial infarction or and mortality.

A retrospective comparison of mortality in critically ill hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent.

OBJECTIVES: To compare acute mortality in critically ill hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent (UCA). BACKGROUND: Because of serious cardiopulmonary reactions reported immediately after administration of perflutren-containing UCAs, the FDA required a black box safety warning for this class of agents, including perflutren protein-type A microspheres injectable suspension. METHODS: This study used the largest hospital service-level database in the U.S. All adult patients undergoing in-patient echocardiography between January 2003 and October 2005 were identified (n = 2,588,722, of which 22,499 received perflutren protein-type A microspheres injectable suspension). Of the 22,499 contrast echocardiography patients, 2,900 had diagnoses meeting criteria for critical illness (heart failure, acute myocardial infarction, arrhythmia, respiratory failure, pulmonary embolism, emphysema, and pulmonary hypertension). To control for the differences between the contrast and noncontrast patients, we used propensity score matching. Variables used in the construction of the propensity score included comorbidities, demographic factors, hospital-specific factors, level of care, and mechanical ventilation status. Patients receiving contrast echocardiography were matched to 4 control patients who received noncontrast echocardiography. Conditional logistic regression was used to estimate mortality effects. RESULTS: There were 167 deaths in the study among critically ill patients, 38 of 2,900 from the contrast group and 129 of 11,600 from the control group. The contrast agent was not associated with an increase in same-day mortality (odds ratio: 1.18; 95% confidence interval: 0.82 to 1.71; p = 0.37). Before matching, contrast patients showed greater morbidity than noncontrast patients (Deyo-Charlson comorbidity score 2.45 vs. 2.25, p < 0.0001). After propensity score matching, these differences were significantly reduced, showing that both groups were well balanced. CONCLUSIONS: There is no increase in mortality in critically ill patients undergoing echocardiography with the UCA compared with case-matched control patients.

Ultrasound contrast agents: balancing safety versus efficacy.

In October, 2007, the FDA issued a new 'black box' warning, several new disease state contraindications and a mandated 30-min post-procedure monitoring period for the ultrasound contrast agents Definity (perflutren lipid microsphere injectable suspension, Lantheus Medical Imaging, North Billerica, MA, USA) and Optison (perflutren protein type A microspheres for injectable suspension, GE Healthcare, Buckinghamshire, UK). These labeling changes were largely secondary to reports of 4 patient deaths, and approximately 190 other 'serious cardiopulmonary reactions' that were temporally related but not clearly causally attributable to Definity administration. Contrast agent use in the US plummeted in the immediate aftermath of this FDA action, with many hospitals, physician offices and outpatient imaging centers suspending contrast echocardiography altogether. This review will focus on the immediate response from the international physician community, new contrast agent safety data published within the past year, results of a special meeting of the FDA Cardio-Renal panel devoted to contrast agent safety in June 2008, recently issued revised product labeling for both agents and future prospects for contrast echocardiography.