St. Francis Hospital

BACKGROUND: Unsustained ventricular tachycardia in patients with previous myocardial infarction and left ventricular dysfunction is associated with a two-year mortality rate of about 30 percent. We studied whether prophylactic therapy with an implanted cardioverter-defibrillator, as compared with conventional medical therapy, would improve survival in this high-risk group of patients. METHODS: Over the course of five years, 196 patients in New York Heart Association functional class I, II, or III with prior myocardial infarction; a left ventricular ejection fraction < or = 0.35; a documented episode of asymptomatic unsustained ventricular tachycardia; and inducible, nonsuppressible ventricular tachyarrhythmia on electrophysiologic study were randomly assigned to receive an implanted defibrillator (n = 95) or conventional medical therapy (n=101). We used a two-sided sequential design with death from any cause as the end point. RESULTS: The base-line characteristics of the two treatment groups were similar. During an average follow-up of 27 months, there were 15 deaths in the defibrillator group (11 from cardiac causes) and 39 deaths in the conventional-therapy group (27 from cardiac causes) (hazard ratio for overall mortality, 0.46; 95 percent confidence interval, 0.26 to 0.82; P=0.009). There was no evidence that amiodarone, beta-blockers, or any other antiarrhythmic therapy had a significant influence on the observed hazard ratio. CONCLUSIONS: In patients with a prior myocardial infarction who are at high risk for ventricular tachyarrhythmia, prophylactic therapy with an implanted defibrillator leads to improved survival as compared with conventional medical therapy.

BACKGROUND: We compared transcatheter aortic-valve replacement (TAVR), using a self-expanding transcatheter aortic-valve bioprosthesis, with surgical aortic-valve replacement in patients with severe aortic stenosis and an increased risk of death during surgery. METHODS: We recruited patients with severe aortic stenosis who were at increased surgical risk as determined by the heart team at each study center. Risk assessment included the Society of Thoracic Surgeons Predictor Risk of Mortality estimate and consideration of other key risk factors. Eligible patients were randomly assigned in a 1:1 ratio to TAVR with the self-expanding transcatheter valve (TAVR group) or to surgical aortic-valve replacement (surgical group). The primary end point was the rate of death from any cause at 1 year, evaluated with the use of both noninferiority and superiority testing. RESULTS: A total of 795 patients underwent randomization at 45 centers in the United States. In the as-treated analysis, the rate of death from any cause at 1 year was significantly lower in the TAVR group than in the surgical group (14.2% vs. 19.1%), with an absolute reduction in risk of 4.9 percentage points (upper boundary of the 95% confidence interval, -0.4; P<0.001 for noninferiority; P = 0.04 for superiority). The results were similar in the intention-to-treat analysis. In a hierarchical testing procedure, TAVR was noninferior with respect to echocardiographic indexes of valve stenosis, functional status, and quality of life. Exploratory analyses suggested a reduction in the rate of major adverse cardiovascular and cerebrovascular events and no increase in the risk of stroke. CONCLUSIONS: In patients with severe aortic stenosis who are at increased surgical risk, TAVR with a self-expanding transcatheter aortic-valve bioprosthesis was associated with a significantly higher rate of survival at 1 year than surgical aortic-valve replacement. (Funded by Medtronic; U.S. CoreValve High Risk Study ClinicalTrials.gov number, NCT01240902.).

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

BACKGROUND: Patients with nonischemic dilated cardiomyopathy are at substantial risk for sudden death from cardiac causes. However, the value of prophylactic implantation of an implantable cardioverter-defibrillator (ICD) to prevent sudden death in such patients is unknown. METHODS: We enrolled 458 patients with nonischemic dilated cardiomyopathy, a left ventricular ejection fraction of less than 36 percent, and premature ventricular complexes or nonsustained ventricular tachycardia. A total of 229 patients were randomly assigned to receive standard medical therapy, and 229 to receive standard medical therapy plus a single-chamber ICD. RESULTS: Patients were followed for a mean (+/-SD) of 29.0+/-14.4 months. The mean left ventricular ejection fraction was 21 percent. The vast majority of patients were treated with angiotensin-converting-enzyme (ACE) inhibitors (86 percent) and beta-blockers (85 percent). There were 68 deaths: 28 in the ICD group, as compared with 40 in the standard-therapy group (hazard ratio, 0.65; 95 percent confidence interval, 0.40 to 1.06; P=0.08). The mortality rate at two years was 14.1 percent in the standard-therapy group (annual mortality rate, 7 percent) and 7.9 percent in the ICD group. There were 17 sudden deaths from arrhythmia: 3 in the ICD group, as compared with 14 in the standard-therapy group (hazard ratio, 0.20; 95 percent confidence interval, 0.06 to 0.71; P=0.006). CONCLUSIONS: In patients with severe, nonischemic dilated cardiomyopathy who were treated with ACE inhibitors and beta-blockers, the implantation of a cardioverter-defibrillator significantly reduced the risk of sudden death from arrhythmia and was associated with a nonsignificant reduction in the risk of death from any cause.

BACKGROUND: inhibitor after a minimum period of dual antiplatelet therapy is an emerging approach to reduce the risk of bleeding after percutaneous coronary intervention (PCI). METHODS: In a double-blind trial, we examined the effect of ticagrelor alone as compared with ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. After 3 months of treatment with ticagrelor plus aspirin, patients who had not had a major bleeding event or ischemic event continued to take ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. We also evaluated the composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, using a noninferiority hypothesis with an absolute margin of 1.6 percentage points. RESULTS: We enrolled 9006 patients, and 7119 underwent randomization after 3 months. Between randomization and 1 year, the incidence of the primary end point was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin (hazard ratio, 0.56; 95% confidence interval [CI], 0.45 to 0.68; P<0.001). The difference in risk between the groups was similar for BARC type 3 or 5 bleeding (incidence, 1.0% among patients receiving ticagrelor plus placebo and 2.0% among patients receiving ticagrelor plus aspirin; hazard ratio, 0.49; 95% CI, 0.33 to 0.74). The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (difference, -0.06 percentage points; 95% CI, -0.97 to 0.84; hazard ratio, 0.99; 95% CI, 0.78 to 1.25; P<0.001 for noninferiority). CONCLUSIONS: Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke. (Funded by AstraZeneca; TWILIGHT ClinicalTrials.gov number, NCT02270242.).

BACKGROUND: The biological basis of frailty has been difficult to establish owing to the lack of a standard definition, its complexity, and its frequent coexistence with illness. OBJECTIVE: To establish the biological correlates of frailty in the presence and absence of concurrent cardiovascular disease and diabetes mellitus. METHODS: Participants were 4735 community-dwelling adults 65 years and older. Frail, intermediate, and nonfrail subjects were identified by a validated screening tool and exclusion criteria. Bivariate relationships between frailty level and physiological measures were evaluated by Pearson chi2 tests for categorical variables and analysis of variance F tests for continuous variables. Multinomial logistic regression was performed to evaluate multivariable relationships between frailty status and physiological measures. RESULTS: Of 4735 Cardiovascular Health Study participants, 299 (6.3%) were identified as frail, 2147 (45.3%) as intermediate, and 2289 (48.3%) as not frail. Frail vs nonfrail participants had increased mean +/- SD levels of C-reactive protein (5.5 +/- 9.8 vs 2.7 +/- 4.0 mg/L), factor VIII (13 790 +/- 4480 vs 11 860 +/- 3460 mg/dL), and, in a smaller subset, D dimer (647 +/- 1033 vs 224 +/- 258 ng/mL) (P< or =.001 for all, chi2 test for trend). These differences persisted when individuals with cardiovascular disease and diabetes were excluded and after adjustment for age, sex, and race. CONCLUSIONS: These findings support the hypothesis that there is a specific physiological basis to the geriatric syndrome of frailty that is characterized in part by increased inflammation and elevated markers of blood clotting and that these physiological differences persist when those with diabetes and cardiovascular disease are excluded.

ST-Segment Elevation in Covid-19 Eighteen patients with Covid-19 presented with ST-segment elevation on ECG or had it develop during hospitalization. Eight patients received a diagnosis of acute my...

BACKGROUND: Frail health in old age has been conceptualized as a loss of physiologic reserve associated with loss of lean mass, neuroendocrine dysregulation, and immune dysfunction. Little work has been done to define frailty and describe the underlying pathophysiology. METHODS: Frailty status was defined in participants of the Cardiovascular Health Study (CHS), a cohort of 5,201 community-dwelling older adults, based on the presence of three out of five clinical criteria. The five criteria included self-reported weight loss, low grip strength, low energy, slow gait speed, and low physical activity. We examined the spectrum of clinical and subclinical cardiovascular disease in those who were frail (3/5 criteria) or of intermediate frailty status (1 or 2/5 criteria), compared to those who were not frail (0/5). We hypothesized that the severity of frailty would be related to a higher prevalence of reported cardiovascular disease (CVD), as well as to a greater extent of CVD, measured by noninvasive testing. RESULTS: Of 4,735 eligible participants, 2,289 (48%) were not frail, 299 (6%) were frail, and 2.147 (45%) were of intermediate frailty status. Those who were frail were older (77.2 yrs) compared to those who were not frail (71.5 yrs) or intermediate (73.4 yrs) (p < .001). Frailty status was associated with clinical CVD and most strongly with congestive heart failure (odds ratio [OR] = 7.51 (95% confidence interval [CI] = 4.66-12.12). In those without a history of a CVD event (n = 1.259), frailty was associated with many noninvasive measures of CVD. Those with carotid stenosis >75% (adjusted OR = 3.41), ankle-arm index <0.8 (adjusted OR = 3.17) or 0.8-0.9 (adjusted OR = 2.01), major electrocardiography (ECG) abnormalities (adjusted OR = 1.58), greater left ventricular (LV) mass by echocardiography (adjusted OR = 1.16), and higher degree of infarct-like lesions in the brain (adjusted OR = 1.71), were more likely to be frail compared to those who were not frail. The overall associations of each of these noninvasive measures of CVD with frailty level were significant (all p < .05). CONCLUSIONS: Cardiovascular disease was associated with an increased likelihood of frail health. In those with no history of CVD, the extent of underlying cardiovascular disease measured by carotid ultrasound and ankle-arm index, LV hypertrophy by ECG and echocardiography, was related to frailty. Infarct-like lesions in the brain on magnet resonance imaging were related to frailty as well.

BACKGROUND: Indications for cardiac-resynchronization therapy (CRT) in patients with heart failure include a prolonged QRS interval (> or =120 msec), in addition to other functional criteria. Some patients with narrow QRS complexes have echocardiographic evidence of left ventricular mechanical dyssynchrony and may also benefit from CRT. METHODS: We enrolled 172 patients who had a standard indication for an implantable cardioverter-defibrillator. Patients received the CRT device and were randomly assigned to the CRT group or to a control group (no CRT) for 6 months. The primary end point was the proportion of patients with an increase in peak oxygen consumption of at least 1.0 ml per kilogram of body weight per minute during cardiopulmonary exercise testing at 6 months. RESULTS: At 6 months, the CRT group and the control group did not differ significantly in the proportion of patients with the primary end point (46% and 41%, respectively). In a prespecified subgroup with a QRS interval of 120 msec or more, the peak oxygen consumption increased in the CRT group (P=0.02), but it was unchanged in a subgroup with a QRS interval of less than 120 msec (P=0.45). There were 24 heart-failure events requiring intravenous therapy in 14 patients in the CRT group (16.1%) and 41 events in 19 patients in the control group (22.3%), but the difference was not significant. CONCLUSIONS: CRT did not improve peak oxygen consumption in patients with moderate-to-severe heart failure, providing evidence that patients with heart failure and narrow QRS intervals may not benefit from CRT. (ClinicalTrials.gov number, NCT00132977 [ClinicalTrials.gov].).

BACKGROUND: There is substantial evidence that coronary calcification, a marker for the presence and quantity of coronary atherosclerosis, is higher in US whites than blacks; however, there have been no large population-based studies comparing coronary calcification among US ethnic groups. METHODS AND RESULTS: Using computed tomography, we measured coronary calcification in 6814 white, black, Hispanic, and Chinese men and women aged 45 to 84 years with no clinical cardiovascular disease who participated in the Multi-Ethnic Study of Atherosclerosis (MESA). The prevalence of coronary calcification (Agatston score >0) in these 4 ethnic groups was 70.4%, 52.1%, 56.5%, and 59.2%, respectively, in men (P<0.001) and 44.6%, 36.5%, 34.9%, and 41.9%, respectively, (P<0.001) in women. After adjustment for age, education, lipids, body mass index, smoking, diabetes, hypertension, treatment for hypercholesterolemia, gender, and scanning center, compared with whites, the relative risks for having coronary calcification were 0.78 (95% CI 0.74 to 0.82) in blacks, 0.85 (95% CI 0.79 to 0.91) in Hispanics, and 0.92 (95% CI 0.85 to 0.99) in Chinese. After similar adjustments, the amount of coronary calcification among those with an Agatston score >0 was greatest among whites, followed by Chinese (77% that of whites; 95% CI 62% to 96%), Hispanics (74%; 95% CI 61% to 90%), and blacks (69%; 95% CI 59% to 80%). CONCLUSIONS: We observed ethnic differences in the presence and quantity of coronary calcification that were not explained by coronary risk factors. Identification of the mechanism underlying these differences would further our understanding of the pathophysiology of coronary calcification and its clinical significance. Data on the predictive value of coronary calcium in different ethnic groups are needed.

BACKGROUND: Elevated renin-angiotensin-aldosterone system activity correlates with left ventricular hypertrophy (LVH) and cardiovascular risk, but the relative contributions of angiotensin II and aldosterone remain unclear. This study compared LVH regression during treatment with the selective aldosterone blocker eplerenone, enalapril, and their combination in patients with hypertension. METHODS AND RESULTS: A 9-month, double-blind, randomized study was performed in 202 patients with LVH and hypertension who received eplerenone 200 mg daily, enalapril 40 mg daily, or eplerenone 200 mg and enalapril 10 mg daily. At week 8, hydrochlorothiazide 12.5 to 25 mg and/or amlodipine 10 mg was added if diastolic blood pressure was >90 mm Hg. Change in left ventricular (LV) mass as assessed by MRI was the primary end point. Change in blood pressure, renin-angiotensin-aldosterone system hormones, albuminuria, and safety were also assessed. Eplerenone significantly reduced LV mass from baseline (-14.5+/-3.36 g; n=50) similarly to enalapril (-19.7+/-3.20 g; n=54; P=0.258), but eplerenone/enalapril (-27.2+/-3.39 g; n=49) was more effective than eplerenone alone (P=0.007). All treatments reduced systolic blood pressure and diastolic blood pressure from baseline (eplerenone, -23.8 and -11.9 mm Hg; enalapril, -24.7 and -13.4 mm Hg; and eplerenone/enalapril, -28.7 and -14.4 mm Hg, P=0.048, in systolic blood pressure compared with eplerenone alone). Cough was more common with enalapril than with eplerenone (P=0.033), and elevated potassium was more common with eplerenone. CONCLUSIONS: Eplerenone was as effective as enalapril in LVH regression and blood pressure control. The combination of eplerenone and enalapril was more effective in reducing LV mass and systolic blood pressure than eplerenone alone.

BACKGROUND: A previous analysis in this trial showed that among patients with severe, symptomatic aortic stenosis who were at low surgical risk, the rate of the composite end point of death, stroke, or rehospitalization at 1 year was significantly lower with transcatheter aortic-valve replacement (TAVR) than with surgical aortic-valve replacement. Longer-term outcomes are unknown. METHODS: We randomly assigned patients with severe, symptomatic aortic stenosis and low surgical risk to undergo either TAVR or surgery. The first primary end point was a composite of death, stroke, or rehospitalization related to the valve, the procedure, or heart failure. The second primary end point was a hierarchical composite that included death, disabling stroke, nondisabling stroke, and the number of rehospitalization days, analyzed with the use of a win ratio analysis. Clinical, echocardiographic, and health-status outcomes were assessed through 5 years. RESULTS: A total of 1000 patients underwent randomization: 503 patients were assigned to undergo TAVR, and 497 to undergo surgery. A component of the first primary end point occurred in 111 of 496 patients in the TAVR group and in 117 of 454 patients in the surgery group (Kaplan-Meier estimates, 22.8% in the TAVR group and 27.2% in the surgery group; difference, -4.3 percentage points; 95% confidence interval [CI], -9.9 to 1.3; P = 0.07). The win ratio for the second primary end point was 1.17 (95% CI, 0.90 to 1.51; P = 0.25). The Kaplan-Meier estimates for the components of the first primary end point were as follows: death, 10.0% in the TAVR group and 8.2% in the surgery group; stroke, 5.8% and 6.4%, respectively; and rehospitalization, 13.7% and 17.4%. The hemodynamic performance of the valve, assessed according to the mean (±SD) valve gradient, was 12.8±6.5 mm Hg in the TAVR group and 11.7±5.6 mm Hg in the surgery group. Bioprosthetic-valve failure occurred in 3.3% of the patients in the TAVR group and in 3.8% of those in the surgery group. CONCLUSIONS: Among low-risk patients with severe, symptomatic aortic stenosis who underwent TAVR or surgery, there was no significant between-group difference in the two primary composite outcomes. (Funded by Edwards Lifesciences; PARTNER 3 ClinicalTrials.gov number, NCT02675114.).

BACKGROUND: Coronary electron beam computed tomography (EBCT) detects atherosclerotic coronary artery disease by measuring calcium deposition in the walls of coronary arteries. EBCT-derived coronary artery calcium (CAC) scores correlate with the severity of underlying coronary artery disease. METHODS AND RESULTS: We followed 1173 asymptomatic patients who underwent EBCT between September 1993 and March 1994. During average follow-up of 19 months, 18 subjects had 26 cardiovascular events: 1 death, 7 myocardial infarctions, 8 coronary artery bypass graft procedures, 9 coronary angioplasties, and 1 nonhemorrhagic stroke. For CAC score thresholds of 100, 160, and 680, EBCT had sensitivities of 89%, 89%, and 50% and specificities of 77%, 82%, and 95%, respectively. Odds ratios ranged from 20.0 to 35.4 (P < .0001 for all). CONCLUSIONS: Coronary EBCT predicts future atherosclerotic cardiovascular disease events in asymptomatic subjects.

BACKGROUND: Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS: We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS: At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03). CONCLUSIONS: Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).

Objective: To establish evidence-based guidelines for the use of bedside cardiac ultrasound, echocardiography, in the ICU and equivalent care sites. Methods: Grading of Recommendations, Assessment, Development and Evaluation system was used to rank the “levels” of quality of evidence into high (A), moderate (B), or low (C) and to determine the “strength” of recommendations as either strong (strength class 1) or conditional/weak (strength class 2), thus generating six “grades” of recommendations (1A–1B–1C–2A–2B–2C). Grading of Recommendations, Assessment, Development and Evaluation was used for all questions with clinically relevant outcomes. RAND Appropriateness Method, incorporating the modified Delphi technique, was used in formulating recommendations related to terminology or definitions or in those based purely on expert consensus. The process was conducted by teleconference and electronic-based discussion, following clear rules for establishing consensus and agreement/disagreement. Individual panel members provided full disclosure and were judged to be free of any commercial bias. Results: Forty-five statements were considered. Among these statements, six did not achieve agreement based on RAND appropriateness method rules (majority of at least 70%). Fifteen statements were approved as conditional recommendations (strength class 2). The rest (24 statements) were approved as strong recommendations (strength class 1). Each recommendation was also linked to its level of quality of evidence and the required level of echo expertise of the intensivist. Key recommendations, listed by category, included the use of cardiac ultrasonography to assess preload responsiveness in mechanically ventilated (1B) patients, left ventricular (LV) systolic (1C) and diastolic (2C) function, acute cor pulmonale (ACP) (1C), pulmonary hypertension (1B), symptomatic pulmonary embolism (PE) (1C), right ventricular (RV) infarct (1C), the efficacy of fluid resuscitation (1C) and inotropic therapy (2C), presence of RV dysfunction (2C) in septic shock, the reason for cardiac arrest to assist in cardiopulmonary resuscitation (1B–2C depending on rhythm), status in acute coronary syndromes (ACS) (1C), the presence of pericardial effusion (1C), cardiac tamponade (1B), valvular dysfunction (1C), endocarditis in native (2C) or mechanical valves (1B), great vessel disease and injury (2C), penetrating chest trauma (1C) and for use of contrast (1B–2C depending on indication). Finally, several recommendations were made regarding the use of bedside cardiac ultrasound in pediatric patients ranging from 1B for preload responsiveness to no recommendation for RV dysfunction. Conclusions: There was strong agreement among a large cohort of international experts regarding several class 1 recommendations for the use of bedside cardiac ultrasound, echocardiography, in the ICU. Evidence-based recommendations regarding the appropriate use of this technology are a step toward improving patient outcomes in relevant patients and guiding appropriate integration of ultrasound into critical care practice.

Background: Outcome trials in patients with type 2 diabetes mellitus have demonstrated reduced hospitalizations for heart failure (HF) with sodium-glucose co-transporter-2 inhibitors. However, few of these patients had HF, and those that did were not well-characterized. Thus, the effects of sodium-glucose co-transporter-2 inhibitors in patients with established HF with reduced ejection fraction, including those with and without type 2 diabetes mellitus, remain unknown. Methods: DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients with HF with Reduced Ejection Fraction) was an investigator-initiated, multi-center, randomized controlled trial of HF patients with left ventricular ejection fraction ≤40%, New York Heart Association (NYHA) class II-III, estimated glomerular filtration rate ≥30 mL/min/1.73m 2 , and elevated natriuretic peptides. In total, 263 patients were randomized to dapagliflozin 10 mg daily or placebo for 12 weeks. Dual primary outcomes were (1) mean NT-proBNP (N-terminal pro b-type natriuretic peptide) and (2) proportion of patients with ≥5-point increase in HF disease-specific health status on the Kansas City Cardiomyopathy Questionnaire overall summary score, or a ≥20% decrease in NT-proBNP. Results: Patient characteristics reflected stable, chronic HF with reduced ejection fraction with high use of optimal medical therapy. There was no significant difference in average 6- and 12-week adjusted NT-proBNP with dapagliflozin versus placebo (1133 pg/dL (95% CI 1036–1238) vs 1191 pg/dL (95% CI 1089–1304), P =0.43). For the second dual-primary outcome of a meaningful improvement in Kansas City Cardiomyopathy Questionnaire overall summary score or NT-proBNP, 61.5% of dapagliflozin-treated patients met this end point versus 50.4% with placebo (adjusted OR 1.8, 95% CI 1.03-3.06, nominal P =0.039). This was attributable to both higher proportions of patients with ≥5-point improvement in Kansas City Cardiomyopathy Questionnaire overall summary score (42.9 vs 32.5%, adjusted OR 1.73, 95% CI 0.98–3.05), and ≥20% reduction in NT-proBNP (44.0 vs 29.4%, adjusted OR 1.9, 95% CI 1.1–3.3) by 12 weeks. Results were consistent among patients with or without type 2 diabetes mellitus, and other prespecified subgroups (all P values for interaction=NS). Conclusions: In patients with heart failure and reduced ejection fraction, use of dapagliflozin over 12 weeks did not affect mean NT-proBNP but increased the proportion of patients experiencing clinically meaningful improvements in HF-related health status or natriuretic peptides. Benefits of dapagliflozin on clinically meaningful HF measures appear to extend to patients without type 2 diabetes mellitus. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02653482.

BACKGROUND: The feasibility of intravascular lithotripsy (IVL) for modification of severe coronary artery calcification (CAC) was demonstrated in the Disrupt CAD I study (Disrupt Coronary Artery Disease). We next sought to confirm the safety and effectiveness of IVL for these lesions. METHODS: The Disrupt CAD II study was a prospective multicenter, single-arm post-approval study conducted at 15 hospitals in 9 countries. Patients with severe CAC with a clinical indication for revascularization underwent vessel preparation for stent implantation with IVL. The primary end point was in-hospital major adverse cardiac events (cardiac death, myocardial infarction, or target vessel revascularization). An optical coherence tomography substudy was performed to evaluate the mechanism of action of IVL, quantifying CAC characteristics and calcium plaque fracture. Independent core laboratories adjudicated angiography and optical coherence tomography, and an independent clinical events committee adjudicated major adverse cardiac events. RESULTS: Between May 2018 and March 2019, 120 patients were enrolled. Severe CAC was present in 94.2% of lesions. Successful delivery and use of the IVL catheter was achieved in all patients. The post-IVL angiographic acute luminal gain was 0.83±0.47 mm, and residual stenosis was 32.7±10.4%, which further decreased to 7.8±7.1% after drug-eluting stent implantation. The primary end point occurred in 5.8% of patients, consisting of 7 non-Q-wave myocardial infarctions. There was no procedural abrupt closure, slow or no reflow, or perforations. In 47 patients with post-percutaneous coronary intervention optical coherence tomography, calcium fracture was identified in 78.7% of lesions with 3.4±2.6 fractures per lesion, measuring 5.5±5.0 mm in length. CONCLUSIONS: In patients with severe CAC who require coronary revascularization, IVL was safely performed with high procedural success and minimal complications and resulted in substantial calcific plaque fracture in most lesions. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03328949.

BACKGROUND: Data from a 5-year follow-up of outcomes after transcatheter edge-to-edge repair of severe mitral regurgitation, as compared with outcomes after maximal doses of guideline-directed medical therapy alone, in patients with heart failure are now available. METHODS: We randomly assigned patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy to undergo transcatheter edge-to-edge repair plus receive medical therapy (device group) or to receive medical therapy alone (control group) at 78 sites in the United States and Canada. The primary effectiveness end point was all hospitalizations for heart failure through 2 years of follow-up. The annualized rate of all hospitalizations for heart failure, all-cause mortality, the risk of death or hospitalization for heart failure, and safety, among other outcomes, were assessed through 5 years. RESULTS: Of the 614 patients enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of hospitalization for heart failure through 5 years was 33.1% per year in the device group and 57.2% per year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.41 to 0.68). All-cause mortality through 5 years was 57.3% in the device group and 67.2% in the control group (hazard ratio, 0.72; 95% CI, 0.58 to 0.89). Death or hospitalization for heart failure within 5 years occurred in 73.6% of the patients in the device group and in 91.5% of those in the control group (hazard ratio, 0.53; 95% CI, 0.44 to 0.64). Device-specific safety events within 5 years occurred in 4 of 293 treated patients (1.4%), with all the events occurring within 30 days after the procedure. CONCLUSIONS: Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite guideline-directed medical therapy, transcatheter edge-to-edge repair of the mitral valve was safe and led to a lower rate of hospitalization for heart failure and lower all-cause mortality through 5 years of follow-up than medical therapy alone. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079.).

OBJECTIVES: The ORBIT II (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) trial evaluated the safety and efficacy of the coronary Orbital Atherectomy System (OAS) to prepare de novo, severely calcified coronary lesions for stent placement. BACKGROUND: Despite advances in interventional techniques, treatment of calcified coronary lesions remains a challenge. Stent placement in these lesions may result in stent underexpansion, malapposition, and procedural complications. METHODS: ORBIT II is a prospective, multicenter, nonblinded clinical trial that enrolled 443 consecutive patients with severely calcified coronary lesions at 49 U.S. sites from May 25, 2010, to November 26, 2012. Investigators used the centrifugal action of the OAS diamond-coated crown to modify calcified lesions prior to stent placement. RESULTS: The pre-procedure mean minimal lumen diameter of 0.5 mm increased to 2.9 mm after the procedure. The primary safety endpoint was 89.6% freedom from 30-day major adverse cardiac events compared with the performance goal of 83%. The primary efficacy endpoint (residual stenosis <50% post-stent without in-hospital major adverse cardiac events) was 88.9% compared with the performance goal of 82%. Stent delivery occurred successfully in 97.7% of cases with <50% stenosis in 98.6% of subjects. Low rates of in-hospital Q-wave myocardial infarction (0.7%), cardiac death (0.2%), and target vessel revascularization (0.7%) were reported. CONCLUSIONS: The ORBIT II coronary OAS trial met both the primary safety and efficacy endpoints by significant margins. Preparation of severely calcified plaque with the OAS not only helped facilitate stent delivery, but improved both acute and 30-day clinical outcomes compared with the outcomes of historic control subjects in this difficult-to-treat patient population. (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions [ORBIT II]; NCT01092416).

BACKGROUND: Ventricular tachyarrhythmias long enough to cause implantable cardioverter defibrillator (ICD) shocks are generally thought to progress to cardiac arrest. In previous ICD trials, shocks have been considered an appropriate surrogate for sudden cardiac death (SCD) because the number of shocks has been thought to be equivalent to the mortality excess in patients without ICDs. The practice of equating ICD shocks with mortality is controversial and has not been validated critically. METHODS AND RESULTS: The Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial was a prospective, randomized, multicenter trial of ICD therapy in 458 patients with nonischemic cardiomyopathy. Patients were randomized to receive standard medical therapy (STD) or STD plus an ICD. Shock electrograms were reviewed, and the cause of death was evaluated by a separate blinded events committee. There were 15 SCD or cardiac arrests in the STD group and only 3 in the ICD arm. In contrast, of the 229 patients randomized to an ICD, 33 received 70 appropriate ICD shocks. Patients in the ICD arm were more likely to have an arrhythmic event (ICD shock plus SCD) than patients in the STD arm (hazard ratio 2.12, 95% CI 1.153 to 3.893, P=0.013). The number of arrhythmic events when one includes syncope as a potential arrhythmic event was similar in both groups (hazard ratio 1.20, 95% CI 0.774 to 1.865, P=0.414). Approximately the same number of total events was noted in each arm when we compared syncope plus SCD/cardiac arrest in the STD arm with SCD plus ICD shocks plus syncope in the ICD arm. CONCLUSIONS: Appropriate ICD shocks occur more frequently than SCD in patients with nonischemic cardiomyopathy. This suggests that episodes of nonsustained ventricular tachycardia frequently terminate spontaneously in such patients.