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The efficacy and safety of sacubitril/valsartan in patients hospitalized with heart failure (HF) across the spectrum of left ventricular ejection fraction (EF) has not been described. Data from randomized trials of sacubitril/valsartan in HF patients with EF ≤40% (PIONEER-HF [Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode] trial) and >40% (PARAGLIDE-HF [Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF] trial) following recent worsening heart failure (WHF) were pooled to examine treatment effect across the EF spectrum. The PIONEER-HF and PARAGLIDE-HF trials were double-blind, randomized trials of sacubitril/valsartan vs control therapy (enalapril or valsartan, respectively). All participants in the PIONEER-HF trial and 69.5% in the PARAGLIDE-HF trial were enrolled during hospitalization for HF after stabilization. The remainder in the PARAGLIDE-HF trial were enrolled ≤30 days after a WHF event. The primary endpoint of both trials was time-averaged proportional change in N-terminal pro–B-type natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8. Adjudicated clinical endpoints were analyzed through the end of follow-up, adjusting for trial. The pooled analysis included 1,347 patients (881 from PIONEER-HF, 466 from PARAGLIDE-HF). Baseline characteristics included median age 66 years, 36% women, 31% Black, 34% de novo HF, and median EF 30%. The reduction in NT-proBNP was 24% greater with sacubitril/valsartan vs control therapy (n = 1,130; ratio of change = 0.76; 95% CI: 0.69-0.83; P < 0.0001). Cardiovascular death or hospitalization for HF was reduced by 30% with sacubitril/valsartan vs control therapy (HR: 0.70; 95% CI: 0.54-0.91; P = 0.0077). This effect was consistent across the spectrum of EF ≤60%. Sacubitril/valsartan increased symptomatic hypotension (risk ratio: 1.35; 95% CI: 1.05-1.72). In patients stabilized after WHF, sacubitril/valsartan led to a greater reduction in plasma NT-proBNP and improved clinical outcome compared with control therapy, in particular across the spectrum of EF ≤60%. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890 ; Changes in NT-proBNP, Safety, and Tolerability in HFpEF Patients With a WHF Event [HFpEF Decompensation] Who Have Been Stabilized and Initiated at the Time of or Within 30 Days Post-decompensation [PARAGLIDE-HF]; NCT03988634) [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Loop diuretics are a primary therapy for the symptomatic treatment of heart failure (HF), but whether torsemide improves patient symptoms and quality of life better than furosemide remains unknown. As prespecified secondary end points, the TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) compared the effect of torsemide versus furosemide on patient-reported outcomes among patients with HF. Methods: TRANSFORM-HF was an open-label, pragmatic, randomized trial of 2859 patients hospitalized for HF (regardless of ejection fraction) across 60 hospitals in the United States. Patients were randomly assigned in a 1:1 ratio to a loop diuretic strategy of torsemide or furosemide with investigator-selected dosage. This report examined effects on prespecified secondary end points, which included Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; assessed as adjusted mean difference in change from baseline; range, 0–100 with 100 indicating best health status; clinically important difference, ≥5 points) and Patient Health Questionnaire-2 (range, 0–6; score ≥3 supporting evaluation for depression) over 12 months. Results: Baseline data were available for 2787 (97.5%) patients for KCCQ-CSS and 2624 (91.8%) patients for Patient Health Questionnaire-2. Median (interquartile range) baseline KCCQ-CSS was 42 (27–60) in the torsemide group and 40 (24–59) in the furosemide group. At 12 months, there was no significant difference between torsemide and furosemide in change from baseline in KCCQ-CSS (adjusted mean difference, 0.06 [95% CI, –2.26 to 2.37]; P =0.96) or the proportion of patients with Patient Health Questionnaire-2 score ≥3 (15.1% versus 13.2%: P =0.34). Results for KCCQ-CSS were similar at 1 month (adjusted mean difference, 1.36 [95% CI, –0.64 to 3.36]; P =0.18) and 6-month follow-up (adjusted mean difference, –0.37 [95% CI, –2.52 to 1.78]; P =0.73), and across subgroups by ejection fraction phenotype, New York Heart Association class at randomization, and loop diuretic agent before hospitalization. Irrespective of baseline KCCQ-CSS tertile, there was no significant difference between torsemide and furosemide on change in KCCQ-CSS, all-cause mortality, or all-cause hospitalization. Conclusions: Among patients discharged after hospitalization for HF, a strategy of torsemide compared with furosemide did not improve symptoms or quality of life over 12 months. The effects of torsemide and furosemide on patient-reported outcomes were similar regardless of ejection fraction, previous loop diuretic use, and baseline health status. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296813. [ABSTRACT FROM AUTHOR]

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Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]

Background: Acute decompensated heart failure accounts for more than 1 million hospitalizations in the United States annually. Whether the initiation of sacubitril-valsartan therapy is safe and effective among patients who are hospitalized for acute decompensated heart failure is unknown.Methods: We enrolled patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the United States. After hemodynamic stabilization, patients were randomly assigned to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or enalapril (target dose, 10 mg twice daily). The primary efficacy outcome was the time-averaged proportional change in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration from baseline through weeks 4 and 8. Key safety outcomes were the rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema.Results: Of the 881 patients who underwent randomization, 440 were assigned to receive sacubitril-valsartan and 441 to receive enalapril. The time-averaged reduction in the NT-proBNP concentration was significantly greater in the sacubitril-valsartan group than in the enalapril group; the ratio of the geometric mean of values obtained at weeks 4 and 8 to the baseline value was 0.53 in the sacubitril-valsartan group as compared with 0.75 in the enalapril group (percent change, -46.7% vs. -25.3%; ratio of change with sacubitril-valsartan vs. enalapril, 0.71; 95% confidence interval [CI], 0.63 to 0.81; P<0.001). The greater reduction in the NT-proBNP concentration with sacubitril-valsartan than with enalapril was evident as early as week 1 (ratio of change, 0.76; 95% CI, 0.69 to 0.85). The rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups.Conclusions: Among patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure, the initiation of sacubitril-valsartan therapy led to a greater reduction in the NT-proBNP concentration than enalapril therapy. Rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups. (Funded by Novartis; PIONEER-HF ClinicalTrials.gov number, NCT02554890 .). [ABSTRACT FROM AUTHOR]

The technique of surgical restoration of postischemically dilated left ventricles (SVR) has almost disappeared from operating theaters after the Surgical Treatment of IsChemic Heart failure (STICH) Trial demonstrated no treatment effect in patients with CAD and ejection fraction below 35%. Criticism on the trial was expressed stating that surgical expertise and patient selection (i.e., almost no aneurysm patients included) may have been inadequate to test the procedure s potential. Gaudino and colleagues now propose to conduct an analysis comparing the STICH patient population to a group of comparable SVR patients treated by a center with documented specific expertise for this technique. We here address the background of the trial and the following controversy and suggest a rationale why the suggested analysis has the potential to add valuable information to the field. [ABSTRACT FROM AUTHOR]

The article discusses research published within the issue that evaluated the use of direct soluble guanylate cyclase (SGC) stimulators, vericiguat in VITALITY- heart failure with preserved ejection fraction (HFpEF) and praliciguat in CAPACITY-HFpEF to increase cyclic guanosine monophosphate (cGMP). Topics covered include endothelial inflammation, myocardial contractility and relaxation, and ventricular remodeling, stiffening and hypertrophy.

Background: The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, as compared with medical therapy alone, in patients with coronary artery disease, heart failure, and severe left ventricular systolic dysfunction remains unclear.Methods: From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy alone (medical-therapy group, 602 patients). The primary outcome was death from any cause. Major secondary outcomes included death from cardiovascular causes and death from any cause or hospitalization for cardiovascular causes. The median duration of follow-up, including the current extended-follow-up study, was 9.8 years.Results: A primary outcome event occurred in 359 patients (58.9%) in the CABG group and in 398 patients (66.1%) in the medical-therapy group (hazard ratio with CABG vs. medical therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97; P=0.02 by log-rank test). A total of 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical-therapy group died from cardiovascular causes (hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006 by log-rank test). Death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and in 524 patients (87.0%) in the medical-therapy group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82; P<0.001 by log-rank test).Conclusions: In a cohort of patients with ischemic cardiomyopathy, the rates of death from any cause, death from cardiovascular causes, and death from any cause or hospitalization for cardiovascular causes were significantly lower over 10 years among patients who underwent CABG in addition to receiving medical therapy than among those who received medical therapy alone. (Funded by the National Institutes of Health; STICH [and STICHES] ClinicalTrials.gov number, NCT00023595.). [ABSTRACT FROM AUTHOR]

The highest-risk patients with heart failure with reduced ejection fraction are those with ischemic cardiomyopathy and severe left ventricular systolic dysfunction (ejection fraction ≤35%). The cornerstone of treatment is guideline-driven medical therapy for all patients and implantable device therapy for appropriately selected patients. Surgical revascularization offers the potential for improved survival and quality of life, particularly in patients with more extensive multivessel disease and the greatest degree of left ventricular systolic dysfunction and remodeling. These are also the patients at greatest short-term risk of mortality with coronary artery bypass graft surgery. The short-term risks of surgery need to be balanced against the potential for long-term benefit. This review discusses the evolving data on the role of surgical revascularization, surgical ventricular reconstruction, and mitral valve surgery in this high-risk patient population. [ABSTRACT FROM AUTHOR]

Background: Patients with ischemic left ventricular dysfunction have higher operative risk with coronary artery bypass graft surgery (CABG). However, those whose early risk is surpassed by subsequent survival benefit have not been identified.Objectives: This study sought to examine the impact of anatomic variables associated with poor prognosis on the effect of CABG in ischemic cardiomyopathy.Methods: All 1,212 patients in the STICH (Surgical Treatment of IsChemic Heart failure) surgical revascularization trial were included. Patients had coronary artery disease (CAD) and ejection fraction (EF) of ≤35% and were randomized to receive CABG plus medical therapy or optimal medical therapy (OMT) alone. This study focused on 3 prognostic factors: presence of 3-vessel CAD, EF below the median (27%), and end-systolic volume index (ESVI) above the median (79 ml/m(2)). Patients were categorized as having 0 to 1 or 2 to 3 of these factors.Results: Patients with 2 to 3 prognostic factors (n = 636) had reduced mortality with CABG compared with those who received OMT (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.56 to 0.89; p = 0.004); CABG had no such effect in patients with 0 to 1 factor (HR: 1.08; 95% CI: 0.81 to 1.44; p = 0.591). There was a significant interaction between the number of factors and the effect of CABG on mortality (p = 0.022). Although 30-day risk with CABG was higher, a net beneficial effect of CABG relative to OMT was observed at >2 years in patients with 2 to 3 factors (HR: 0.53; 95% CI: 0.37 to 0.75; p<0.001) but not in those with 0 to 1 factor (HR: 0.88; 95% CI: 0.59 to 1.31; p = 0.535).Conclusions: Patients with more advanced ischemic cardiomyopathy receive greater benefit from CABG. This supports the indication for surgical revascularization in patients with more extensive CAD and worse myocardial dysfunction and remodeling. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595). [ABSTRACT FROM AUTHOR]

Background Patients with ischemic left ventricular dysfunction have higher operative risk with coronary artery bypass graft surgery (CABG). However, those whose early risk is surpassed by subsequent survival benefit have not been identified. Objectives This study sought to examine the impact of anatomic variables associated with poor prognosis on the effect of CABG in ischemic cardiomyopathy. Methods All 1,212 patients in the STICH (Surgical Treatment of IsChemic Heart failure) surgical revascularization trial were included. Patients had coronary artery disease (CAD) and ejection fraction (EF) of ≤35% and were randomized to receive CABG plus medical therapy or optimal medical therapy (OMT) alone. This study focused on 3 prognostic factors: presence of 3-vessel CAD, EF below the median (27%), and end-systolic volume index (ESVI) above the median (79 ml/m²). Patients were categorized as having 0 to 1 or 2 to 3 of these factors. Results Patients with 2 to 3 prognostic factors (n = 636) had reduced mortality with CABG compared with those who received OMT (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.56 to 0.89; p = 0.004); CABG had no such effect in patients with 0 to 1 factor (HR: 1.08; 95% CI: 0.81 to 1.44; p = 0.591). There was a significant interaction between the number of factors and the effect of CABG on mortality (p = 0.022). Although 30-day risk with CABG was higher, a net beneficial effect of CABG relative to OMT was observed at >2 years in patients with 2 to 3 factors (HR: 0.53; 95% CI: 0.37 to 0.75; p<0.001) but not in those with 0 to 1 factor (HR: 0.88; 95% CI: 0.59 to 1.31; p = 0.535). Conclusions Patients with more advanced ischemic cardiomyopathy receive greater benefit from CABG. This supports the indication for surgical revascularization in patients with more extensive CAD and worse myocardial dysfunction and remodeling. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595) [ABSTRACT FROM AUTHOR]

Importance: Mental stress can induce myocardial ischemia and also has been implicated in triggering cardiac events. However, pharmacological interventions aimed at reducing mental stress-induced myocardial ischemia (MSIMI) have not been well studied.Objective: To examine the effects of 6 weeks of escitalopram treatment vs placebo on MSIMI and other psychological stress-related biophysiological and emotional parameters.Design, Setting, and Participants: The REMIT (Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment) study, a randomized, double-blind, placebo-controlled trial of patients with clinically stable coronary heart disease and laboratory-diagnosed MSIMI. Enrollment occurred from July 24, 2007, through August 24, 2011, at a tertiary medical center.Interventions: Eligible participants were randomized 1:1 to receive escitalopram (dose began at 5 mg/d, with titration to 20 mg/d in 3 weeks) or placebo over 6 weeks.Main Outcomes and Measures: Occurrence of MSIMI, defined as development or worsening of regional wall motion abnormality; left ventricular ejection fraction reduction of 8% or more; and/or horizontal or down-sloping ST-segment depression of 1 mm or more in 2 or more leads, lasting for 3 or more consecutive beats, during 1 or more of 3 mental stressor tasks.Results: Of 127 participants randomized to receive escitalopram (n = 64) or placebo (n = 63), 112 (88.2%) completed end point assessments (n = 56 in each group). At the end of 6 weeks, more patients taking escitalopram (34.2% [95% CI, 25.4%-43.0%]) had absence of MSIMI during the 3 mental stressor tasks compared with patients taking placebo (17.5% [95% CI, 10.4%-24.5%]), based on the unadjusted multiple imputation model for intention-to-treat analysis. A significant difference favoring escitalopram was observed (odds ratio, 2.62 [95% CI, 1.06-6.44]). Rates of exercise-induced ischemia were slightly lower at 6 weeks in the escitalopram group (45.8% [95% CI, 36.6%-55.0%]) than in patients receiving placebo (52.5% [95% CI, 43.3%-61.8%]), but this difference was not statistically significant (adjusted odds ratio; 1.24 [95% CI, 0.60-2.58]; P = .56).Conclusions and Relevance: Among patients with stable coronary heart disease and baseline MSIMI, 6 weeks of escitalopram, compared with placebo, resulted in a lower rate of MSIMI. There was no statistically significant difference in exercise-induced ischemia. Replication of these results in multicenter settings and investigations of other medications for reducing MSIMI are needed.Trial Registration: clinicaltrials.gov Identifier: NCT00574847. [ABSTRACT FROM AUTHOR]

The article describes a study that examined the effects of 6 weeks of escitalopram treatment versus placebo on mental stress-induced myocardial ischemia (MSIMI) and other psychological stress-related biophysiological and emotional parameters. It also states that as part of the study, a randomized clinical trial of patients with clinically stable coronary heart disease and laboratory-diagnosed MSIMI was conducted and also states that patients treated with escitalopram, compared with placebo, resulted in a lower rate of MSIMI. It also states that no statistically significant difference was in exercise-induced ischemia.

Background: The role of coronary-artery bypass grafting (CABG) in the treatment of patients with coronary artery disease and heart failure has not been clearly established. Methods: Between July 2002 and May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to medical therapy alone (602 patients) or medical therapy plus CABG (610 patients). The primary outcome was the rate of death from any cause. Major secondary outcomes included the rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes. Results: The primary outcome occurred in 244 patients (41%) in the medical-therapy group and 218 (36%) in the CABG group (hazard ratio with CABG, 0.86; 95% confidence interval [CI], 0.72 to 1.04; P=0.12). A total of 201 patients (33%) in the medical-therapy group and 168 (28%) in the CABG group died from an adjudicated cardiovascular cause (hazard ratio with CABG, 0.81; 95% CI, 0.66 to 1.00; P=0.05). Death from any cause or hospitalization for cardiovascular causes occurred in 411 patients (68%) in the medical-therapy group and 351 (58%) in the CABG group (hazard ratio with CABG, 0.74; 95% CI, 0.64 to 0.85; P<0.001). By the end of the follow-up period (median, 56 months), 100 patients in the medical-therapy group (17%) underwent CABG, and 555 patients in the CABG group (91%) underwent CABG. Conclusions: In this randomized trial, there was no significant difference between medical therapy alone and medical therapy plus CABG with respect to the primary end point of death from any cause. Patients assigned to CABG, as compared with those assigned to medical therapy alone, had lower rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes. (Funded by the National Heart, Lung, and Blood Institute and Abbott Laboratories; STICH ClinicalTrials.gov number, NCT00023595.) N Engl J Med 2011;364:1607-16. [ABSTRACT FROM AUTHOR]

Background: Surgical ventricular reconstruction is a specific procedure designed to reduce left ventricular volume in patients with heart failure caused by coronary artery disease. We conducted a trial to address the question of whether surgical ventricular reconstruction added to coronary-artery bypass grafting (CABG) would decrease the rate of death or hospitalization for cardiac causes, as compared with CABG alone. Methods: Between September 2002 and January 2006, a total of 1000 patients with an ejection fraction of 35% or less, coronary artery disease that was amenable to CABG, and dominant anterior left ventricular dysfunction that was amenable to surgical ventricular reconstruction were randomly assigned to undergo either CABG alone (499 patients) or CABG with surgical ventricular reconstruction (501 patients). The primary outcome was a composite of death from any cause and hospitalization for cardiac causes. The median follow-up was 48 months. Results: Surgical ventricular reconstruction reduced the end-systolic volume index by 19%, as compared with a reduction of 6% with CABG alone. Cardiac symptoms and exercise tolerance improved from baseline to a similar degree in the two study groups. However, no significant difference was observed in the primary outcome, which occurred in 292 patients (59%) who were assigned to undergo CABG alone and in 289 patients (58%) who were assigned to undergo CABG with surgical ventricular reconstruction (hazard ratio for the combined approach, 0.99; 95% confidence interval, 0.84 to 1.17; P=0.90). Conclusions: Adding surgical ventricular reconstruction to CABG reduced the left ventricular volume, as compared with CABG alone. However, this anatomical change was not associated with a greater improvement in symptoms or exercise tolerance or with a reduction in the rate of death or hospitalization for cardiac causes. (ClinicalTrials.gov number, NCT00023595.) N Engl J Med 2009;360:1705-17. [ABSTRACT FROM AUTHOR]

Background How often echocardiography and cardiac catheterization are used to evaluate left ventricular (LV) function in patients with myocardial infarction (MI) and how they are associated with quality of care is unknown. Methods Patients with MI in the Valsartan in Acute Myocardial Infarction (VALIANT) registry were divided into those with (n = 1423) and without (n = 3968) heart failure (HF), and the use of either echocardiography or cardiac catheterization for LV assessment in each group was compared along with associated baseline characteristics. We evaluated the association between LV assessment and discharge medications. Using a multivariable model with a propensity analysis, we evaluated the association of LV assessment with in-hospital outcomes. Results Of the patients with HF, 322 (22.6%) had no LV assessment. Patients with HF with LV assessment were discharged more frequently under treatment with aspirin (81.3% vs 70.0%; P<.001), β-blockers (65.6% vs 56.4%; P = .008), clopidogrel (30.4% vs 14.0%; P<.001), and statins (45.9% vs 34.2%; P<.001). Patients without HF who underwent LV assessment were discharged more frequently under treatment with an angiotensin-converting enzyme inhibitor (53.8% vs 41.5%; P<.001). After adjustment for regional use, other covariates, and revascularization, LV assessment was associated with lower in-hospital mortality in patients with HF (adjusted odds ratio [OR], 0.45; P<.001) and in patients without HF (adjusted OR, 0.30; P<.001). After excluding deaths during the first 2 days, LV assessment remained associated with lower mortality in patients with HF (adjusted OR, 0.59; P = .03) and in patients without HF (adjusted OR, 0.41; P<.001). Conclusion Left ventricular assessment was frequently not performed during the in-hospital stay of patients with acute MI, including those with clinical HF, and its use was associated with better quality of care. [ABSTRACT FROM AUTHOR]

Background: the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial compared outcomes with: (1) angiotensin-converting enzyme inhibition (ACEI) with the reference agent captopril; (2) angiotensin-receptor blockade (ARB) with valsartan; or (3) both in patients with heart failure (HF) and/or left ventricular systolic dysfunction (LVSD) after myocardial infarction (MI). Aims: a goal of this active-control trial was to simulate conditions that would lead current practitioners to use ACEIs. Thus, we compared characteristics of VALIANT patients with those of patients in placebo-controlled trials that established ACEIs as standard treatment. Methods and Results: we collected demographic, clinical, medication and imaging information from 14 703 patients in 24 countries. This high-risk population was a median 65.8 years old, and 31.1% were female. Most (51.8%) showed imaging evidence of LVSD at enrollment. Most (72%) had Killip class≥II HF. Patients received evidence-based therapies at rates similar to those of contemporary MI trials and at an improved rate compared with prior placebo-controlled ACEI trials. Conclusion: VALIANT represents the largest globally representative cohort enrolled with HF and/or LVSD after MI. Patients were similar to those in placebo-controlled ACEI trials while reflecting improvements in evidence-based care. With enrollment complete, VALIANT is poised to define the optimal strategy for renin–angiotensin system blockade after MI to improve cardiovascular outcomes. [Copyright &y& Elsevier]

In this observational treatment comparison in a single center over 25 years, we sought to assess long-term outcomes of coronary artery bypass surgery (CABG) or medical therapy in patients with heart failure, coronary artery disease, and left ventricular systolic dysfunction. The benefit of CABG compared with medical therapy alone in these patients is a source of continuing clinical debate. This analysis considered all patients with New York Heart Association class II or greater symptoms, 1 or more epicardial coronary vessels with a ≥75% stenosis, and a left ventricular ejection fraction <40% who underwent an initial cardiac catheterization at Duke University Medical Center from 1969 to 1994. Patients were classified into the medical therapy group (n = 1,052) or CABG group (n = 339) depending on which therapy they received within 30 days of catheterization. Cardiovascular event and mortality follow-up commenced on the day of CABG, or at catheterization plus 8 days (the mean time to CABG) for the medical therapy arm. A Cox proportional-hazards model was employed to adjust for differences in baseline characteristics. In the first 30 days from baseline, there was an interaction between treatment strategy and number of diseased vessels. Unadjusted, event-free, and adjusted survival strongly favored CABG over medical therapy after 30 days to >10 years regardless of the extent of coronary disease (p <0.001). Thus, regardless of the severity of coronary disease, heart failure symptoms, or ventricular dysfunction, CABG provides extended event-free and survival advantage over medical therapy alone in patients with an ischemic cardiomyopathy. [Copyright &y& Elsevier]

Comments on several medical topics. Development of therapies that only appear to be effective during small trials and the importance of constant testing during uncertainty; Effect of microgravity or gravitational changes on the mineral density of bones, and its possible impact on human space exploration; Discovery of water-channel proteins and the role of water channels in water movement across cell membranes; Steroid therapy for visual loss in patients with giant-cell arteritis.

Aim: The TRANSFORM‐HF trial demonstrated no significant outcome differences between torsemide and furosemide following hospitalization for heart failure (HF), but may have been impacted by non‐adherence to the randomized diuretic. The current study sought to determine the treatment effect of torsemide versus furosemide using an on‐treatment analysis inclusive of all randomized patients except those confirmed non‐adherent to study diuretic. Methods and results: TRANSFORM‐HF was an open‐label, pragmatic randomized trial of 2859 patients hospitalized for HF from June 2018 through March 2022. Patients were randomized to a loop diuretic strategy of torsemide versus furosemide with investigator‐selected dosage. This post‐hoc on‐treatment analysis included all patients alive with either known or unknown diuretic status, and excluded patients confirmed to be non‐adherent to study diuretic. This modified on‐treatment definition was applied separately at time of hospital discharge and 30‐day follow‐up. All‐cause mortality and hospitalization outcomes were assessed over 12 months. Overall, 2570 (89.9%) and 2374 (83.0%) patients were included in on‐treatment analyses at discharge and 30‐day follow‐up, respectively. There was no significant difference in all‐cause mortality between torsemide and furosemide in patients on‐treatment at discharge (17.5% vs. 17.8%; hazard ratio [HR] 1.01 [95% confidence interval [CI] 0.83–1.22], p = 0.96) and at 30‐day follow‐up (14.5% vs. 15.0%; HR 1.02 [95% CI 0.81–1.27], p = 0.90). All‐cause mortality or all‐cause hospitalization was similar between torsemide and furosemide in patients who were on‐treatment at discharge (58.3% vs. 61.3%; HR 0.92 [95% CI 0.82–1.03]) and 30‐day follow‐up (60.9% vs. 64.4%; HR 0.93 [95% CI 0.82–1.05]). In patients who were on‐treatment at 30‐day follow‐up, there were 677 total hospitalizations in the torsemide group and 686 total hospitalizations in the furosemide group (rate ratio 0.99 [95% CI 0.86–1.14], p = 0.87). Conclusions: In TRANSFORM‐HF, a post‐hoc on‐treatment analysis did not meaningfully differ from the original trial results. Among those deemed compliant with the assigned diuretic, there remained no significant difference in mortality or hospitalization after HF hospitalization with a strategy of torsemide versus furosemide. Clinical Trail Registration: ClinicalTrials.gov Identifier: NCT03296813. [ABSTRACT FROM AUTHOR]

Aim: Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all‐cause mortality or hospitalization. Clinicians have traditionally favoured torsemide in the setting of kidney dysfunction due to better oral bioavailability and longer half‐life, but direct supportive evidence is lacking. Methods and results: The TRANSFORM‐HF trial randomized patients hospitalized for HF to a long‐term strategy of torsemide versus furosemide, and enrolled patients across the spectrum of renal function (without dialysis). In this post‐hoc analysis, baseline renal function during the index hospitalization was assessed as categories of estimated glomerular filtration rate (eGFR; <30, 30–<60, ≥60 ml/min/1.73 m2). The interaction between baseline renal function and treatment effect of torsemide versus furosemide was assessed with respect to mortality and hospitalization outcomes, and the change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ‐CSS). Of 2859 patients randomized, 336 (11.8%) had eGFR <30 ml/min/1.73 m2, 1138 (39.8%) had eGFR 30–<60 ml/min/1.73 m2, and 1385 (48.4%) had eGFR ≥60 ml/min/1.73 m2. Baseline eGFR did not modify treatment effects of torsemide versus furosemide on all adverse clinical outcomes including individual components or composites of all‐cause mortality and all‐cause (re)‐hospitalizations, both when assessing eGFR categorically or continuously (p‐value for interaction all >0.108). Similarly, no treatment effect modification by eGFR was found for the change in KCCQ‐CSS (p‐value for interaction all >0.052) when assessing eGFR categorically or continuously. Conclusion: Among patients discharged after hospitalization for HF, there was no significant difference in clinical and patient‐reported outcomes between torsemide and furosemide, irrespective of renal function. [ABSTRACT FROM AUTHOR]

Summary: Iron overload from repeated transfusions has a negative impact on cardiac function, and iron chelation therapy may help prevent cardiac dysfunction in transfusion‐dependent patients with myelodysplastic syndromes (MDS). TELESTO (NCT00940602) was a prospective, placebo‐controlled, randomised study to evaluate the iron chelator deferasirox in patients with low‐ or intermediate‐1–risk MDS and iron overload. Echocardiographic parameters were collected at screening and during treatment. Patients receiving deferasirox experienced a significant decrease in the composite risk of hospitalisation for congestive heart failure (CHF) or worsening of cardiac function (HR = 0.23; 95% CI: 0.05, 0.99; nominal p = 0.0322) versus placebo. No significant differences between the arms were found in left ventricular ejection fraction, ventricular diameter and mass or pulmonary artery pressure. The absolute number of events was low, but the enrolled patients were younger than average for patients with MDS, with no serious cardiac comorbidities and a modest cardiovascular risk profile. These results support the effectiveness of deferasirox in preventing cardiac damage caused by iron overload in this patient population. Identification of patients developing CHF is challenging due to the lack of distinctive echocardiographic features. The treatment of iron overload may be important to prevent cardiac dysfunction in these patients, even those with moderate CHF risk. [ABSTRACT FROM AUTHOR]

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Background: Guidelines recommend 3D echocardiography (3DE) to assess left ventricular ejection fraction (LVEF) on transthoracic echocardiogram (TTE) when possible, but it is unclear which factors are most strongly associated with reporting 3DE LVEF in real‐world practice. Methods: We evaluated 3DE LVEF reporting by age, sex, BMI, TTE location and variation in reporting by sonographer and reader. All TTEs were performed without contrast enhancement agent at a large medical center from 9/2015 to 12/2020 using ultrasound machines capable of 3DE. We used multivariable logistic regression to assess which factors were most associated with reporting 3DE LVEF. Results: Among 35 641 TTEs included in this study, 57.4% were performed on women. 3DE LVEF was reported on 18 391 TTEs (51.6% of cohort; 50.5% for women and 52.4% for men). Portable inpatient TTEs (n = 5569) had the lowest rates of 3DE LVEF reporting (30.9%), while general outpatient TTEs (n = 15 933) had greater reporting (56.9%). Outpatient TTEs with an indication for chemotherapy (n = 3244) had the highest rates of 3DE LVEF (87.2%). The median (IQR) percentage of TTEs reporting 3D LVEF was 52.7% (43.1%–68.1%) among sonographers and 51.6% (46.5%–59.6%) among readers. Among 20082 (56.3%) TTEs with 3DE LVEF measured by sonographers, 91.6% were included by readers in the final report. After adjustment, performing sonographer in the highest reporting quartile was most strongly associated with reporting 3DE LVEF (OR 7.04, 95% CI 6.55–7.56), while an inpatient portable study had the strongest negative association for reporting (OR.38, 95% CI.35–.40). Conclusions: Use of 3DE LVEF in real‐world practice varies substantially based on performing sonographer and is low for hospitalized patients, but can be frequently used for chemotherapy. Initiatives are needed to increase sonographer 3DE acquisition in most clinical settings. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Isosorbide Mononitrate in Heart Failure With Preserved Ejection Fraction," by M. M. Redfield et al., published in the December 10, 2016 issue.

BACKGROUND: Left ventricular (LV) systolic dysfunction is associated with a >8-fold increased risk of heart failure and a 2-fold risk of premature death. The use of ECG signals in screening for LV systolic dysfunction is limited by their availability to clinicians. We developed a novel deep learning-based approach that can use ECG images for the screening of LV systolic dysfunction. METHODS: Using 12-lead ECGs plotted in multiple different formats, and corresponding echocardiographic data recorded within 15 days from the Yale New Haven Hospital between 2015 and 2021, we developed a convolutional neural network algorithm to detect an LV ejection fraction <40%. The model was validated within clinical settings at Yale New Haven Hospital and externally on ECG images from Cedars Sinai Medical Center in Los Angeles, CA; Lake Regional Hospital in Osage Beach, MO; Memorial Hermann Southeast Hospital in Houston, TX; and Methodist Cardiology Clinic of San Antonio, TX. In addition, it was validated in the prospective Brazilian Longitudinal Study of Adult Health. Gradient-weighted class activation mapping was used to localize class-discriminating signals on ECG images. RESULTS: Overall, 385 601 ECGs with paired echocardiograms were used for model development. The model demonstrated high discrimination across various ECG image formats and calibrations in internal validation (area under receiving operation characteristics [AUROCs], 0.91; area under precision-recall curve [AUPRC], 0.55); and external sets of ECG images from Cedars Sinai (AUROC, 0.90 and AUPRC, 0.53), outpatient Yale New Haven Hospital clinics (AUROC, 0.94 and AUPRC, 0.77), Lake Regional Hospital (AUROC, 0.90 and AUPRC, 0.88), Memorial Hermann Southeast Hospital (AUROC, 0.91 and AUPRC 0.88), Methodist Cardiology Clinic (AUROC, 0.90 and AUPRC, 0.74), and Brazilian Longitudinal Study of Adult Health cohort (AUROC, 0.95 and AUPRC, 0.45). An ECG suggestive of LV systolic dysfunction portended >27-fold higher odds of LV systolic dysfunction on transthoracic echocardiogram (odds ratio, 27.5 [95% CI, 22.3-33.9] in the held-out set). Class-discriminative patterns localized to the anterior and anteroseptal leads (V2 and V3), corresponding to the left ventricle regardless of the ECG layout. A positive ECG screen in individuals with an LV ejection fraction =40% at the time of initial assessment was associated with a 3.9-fold increased risk of developing incident LV systolic dysfunction in the future (hazard ratio, 3.9 [95% CI, 3.3-4.7]; median follow-up, 3.2 years). CONCLUSIONS: We developed and externally validated a deep learning model that identifies LV systolic dysfunction from ECG images. This approach represents an automated and accessible screening strategy for LV systolic dysfunction, particularly in low-resource settings. [ABSTRACT FROM AUTHOR]

U.S. guidelines recommend consideration of sacubitril/valsartan in chronic heart failure (HF) and mildly reduced or preserved ejection fraction (EF). Whether initiation is safe and effective in EF >40% after a worsening heart failure (WHF) event is unknown. PARAGLIDE-HF (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF) assessed sacubitril/valsartan vs valsartan in EF >40% following a recent WHF event. PARAGLIDE-HF is a double-blind, randomized controlled trial of sacubitril/valsartan vs valsartan in patients with EF >40% enrolled within 30 days of a WHF event. The primary endpoint was time-averaged proportional change in amino terminal pro–B-type natriuretic peptide (NT-proBNP) from baseline through Weeks 4 and 8. A secondary hierarchical outcome (win ratio) consisted of: 1) cardiovascular death; 2) HF hospitalizations; 3) urgent HF visits; and 4) change in NT-proBNP. In 466 patients (233 sacubitril/valsartan; 233 valsartan), time-averaged reduction in the NT-proBNP was greater with sacubitril/valsartan (ratio of change: 0.85; 95% CI: 0.73-0.999; P = 0.049). The hierarchical outcome favored sacubitril/valsartan but was not significant (unmatched win ratio: 1.19; 95% CI: 0.93-1.52; P = 0.16). Sacubitril/valsartan reduced worsening renal function (OR: 0.61; 95% CI: 0.40-0.93) but increased symptomatic hypotension (OR: 1.73; 95% CI: 1.09-2.76). There was evidence of a larger treatment effect in the subgroup with EF ≤60% for NT-proBNP change (0.78; 95% CI: 0.61-0.98) and the hierarchical outcome (win ratio: 1.46; 95% CI: 1.09-1.95). Among patients with EF >40% stabilized after WHF, sacubitril/valsartan led to greater reduction in plasma NT-proBNP levels and was associated with clinical benefit compared with valsartan alone, despite more symptomatic hypotension. (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF; NCT03988634) [Display omitted] [ABSTRACT FROM AUTHOR]

TRANSFORM-HF set out to investigate a foundational question for the management of patients with heart failure and answered it (albeit with a neutral result). Effect of torsemide vs furosemide after discharge on all-cause mortality in patients hospitalized with heart failure: the TRANSFORM-HF randomized clinical trial. Comment & Response B In Reply b The TRANSFORM-HF investigators thank Dr Wolowich for his comments on our trial.[1] We appreciate his perspectives related to I CYP i sequence variants and a potential impact on torsemide metabolism. [Extracted from the article]

Key Points: Question: Does torsemide reduce all-cause mortality compared with furosemide in patients with heart failure following hospitalization? Findings: In this randomized clinical trial of 2859 patients, 26.1% of patients randomized to torsemide and 26.2% randomized to furosemide died over a median follow-up of 17.4 months without a significant difference between groups. Meaning: Among patients discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months; however, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence. Importance: Although furosemide is the most commonly used loop diuretic in patients with heart failure, some studies suggest a potential benefit for torsemide. Objective: To determine whether torsemide results in decreased mortality compared with furosemide among patients hospitalized for heart failure. Design, Setting, and Participants: TRANSFORM-HF was an open-label, pragmatic randomized trial that recruited 2859 participants hospitalized with heart failure (regardless of ejection fraction) at 60 hospitals in the United States. Recruitment occurred from June 2018 through March 2022, with follow-up through 30 months for death and 12 months for hospitalizations. The final date for follow-up data collection was July 2022. Interventions: Loop diuretic strategy of torsemide (n = 1431) or furosemide (n = 1428) with investigator-selected dosage. Main Outcomes and Measures: The primary outcome was all-cause mortality in a time-to-event analysis. There were 5 secondary outcomes with all-cause mortality or all-cause hospitalization and total hospitalizations assessed over 12 months being highest in the hierarchy. The prespecified primary hypothesis was that torsemide would reduce all-cause mortality by 20% compared with furosemide. Results: TRANSFORM-HF randomized 2859 participants with a median age of 65 years (IQR, 56-75), 36.9% were women, and 33.9% were Black. Over a median follow-up of 17.4 months, a total of 113 patients (53 [3.7%] in the torsemide group and 60 [4.2%] in the furosemide group) withdrew consent from the trial prior to completion. Death occurred in 373 of 1431 patients (26.1%) in the torsemide group and 374 of 1428 patients (26.2%) in the furosemide group (hazard ratio, 1.02 [95% CI, 0.89-1.18]). Over 12 months following randomization, all-cause mortality or all-cause hospitalization occurred in 677 patients (47.3%) in the torsemide group and 704 patients (49.3%) in the furosemide group (hazard ratio, 0.92 [95% CI, 0.83-1.02]). There were 940 total hospitalizations among 536 participants in the torsemide group and 987 total hospitalizations among 577 participants in the furosemide group (rate ratio, 0.94 [95% CI, 0.84-1.07]). Results were similar across prespecified subgroups, including among patients with reduced, mildly reduced, or preserved ejection fraction. Conclusions and Relevance: Among patients discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months. However, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence. Trial Registration: ClinicalTrials.gov Identifier: NCT03296813 This clinical trial compares the efficacy of torsemide vs furosemide in decreasing the risk of death from any cause among patients hospitalized for heart failure (regardless of ejection fraction). [ABSTRACT FROM AUTHOR]

Background: The use of guideline-directed medical therapy (GDMT) is underprescribed in patients with heart failure with reduced ejection fraction (HFrEF).Objectives: This study sought to examine whether targeted and tailored electronic health record (EHR) alerts recommending GDMT in eligible patients with HFrEF improves GDMT use.Methods: PROMPT-HF (PRagmatic trial Of Messaging to Providers about Treatment of Heart Failure) was a pragmatic, EHR-based, cluster-randomized comparative effectiveness trial. A total of 100 providers caring for patients with HFrEF were randomized to either an alert or usual care. The alert notified providers of individualized GDMT recommendations along with patient characteristics. The primary outcome was an increase in the number of GDMT classes prescribed at 30 days postrandomization. Providers were surveyed on knowledge of guidelines and user experience.Results: The study enrolled 1,310 ambulatory patients with HFrEF from April to October 2021. Median age was 72 years; 31% were female; 18% were Black; and median left ventricular ejection fraction was 32%. At baseline, 84% of participants were receiving β-blockers, 71% received a renin-angiotensin-aldosterone system inhibitor, 29% received a mineralocorticoid receptor antagonist, and 11% received a sodium-glucose cotransporter-2 inhibitor. The primary outcome occurred in 176 of 685 (26%) participants in the alert arm vs 117 of 625 (19%) in the usual care arm, thus increasing GDMT class prescription by >40% after alert exposure (adjusted relative risk: 1.41; 95% CI: 1.03-1.93; P = 0.03). The number of patients needed to alert to result in an increase in addition of GDMT classes was 14. A total of 79% of alerted providers agreed that the alert was effective at enabling improved prescription of medical therapy for HF.Conclusions: A real-time, targeted, and tailored EHR-based alerting system for outpatients with HFrEF led to significantly higher rates of GDMT at 30 days when compared with usual care. This low-cost intervention can be rapidly integrated into clinical care and accelerate adoption of high-value therapies in heart failure. (PRagmatic trial Of Messaging to Providers about Treatment of Heart Failure [PROMPT-HF; NCT04514458]). [ABSTRACT FROM AUTHOR]

Background: The STICH (Surgical Treatment for Ischemic Heart Failure) trial compared a strategy of routine coronary artery bypass grafting (CABG) with guideline-based medical therapy for patients with ischemic left ventricular dysfunction.Objective: To describe treatment-related quality-of-life (QOL) outcomes, a major prespecified secondary end point in the STICH trial.Design: Randomized trial. (ClinicalTrials.gov: NCT00023595).Setting: 99 clinical sites in 22 countries.Patients: 1212 patients with a left ventricular ejection fraction of 0.35 or less and coronary artery disease.Intervention: Random assignment to medical therapy alone (602 patients) or medical therapy plus CABG (610 patients).Measurements: A battery of QOL instruments at baseline (98.9% complete) and 4, 12, 24, and 36 months after randomization (collection rates were 80% to 89% of those eligible). The principal prespecified QOL measure was the Kansas City Cardiomyopathy Questionnaire, which assesses the effect of heart failure on patients' symptoms, physical function, social limitations, and QOL.Results: The Kansas City Cardiomyopathy Questionnaire overall summary score was consistently higher (more favorable) in the CABG group than in the medical therapy group by 4.4 points (95% CI, 1.8 to 7.0 points) at 4 months, 5.8 points (CI, 3.1 to 8.6 points) at 12 months, 4.1 points (CI, 1.2 to 7.1 points) at 24 months, and 3.2 points (CI, 0.2 to 6.3 points) at 36 months. Sensitivity analyses to account for the effect of mortality on follow-up QOL measurement were consistent with the primary findings.Limitation: Therapy was not masked.Conclusion: In this cohort of symptomatic high-risk patients with ischemic left ventricular dysfunction and multivessel coronary artery disease, CABG plus medical therapy produced clinically important improvements in quality of life compared with medical therapy alone over 36 months.Primary Funding Source: National Heart, Lung, and Blood Institute. [ABSTRACT FROM AUTHOR]

Background: The STICH (Surgical Treatment for Ischemic Heart Failure) trial compared a strategy of routine coronary artery bypass grafting (CABG) with guideline-based medical therapy for patients with ischemic left ventricular dysfunction. Objective: To describe treatment-related quality-of-life (QOL) outcomes, a major prespecified secondary end point in the STICH trial. Design: Randomized trial. (ClinicalTrials.gov: NCT00023595) Setting: 99 clinical sites in 22 countries. Patients: 1212 patients with a left ventricular ejection fraction of 0.35 or less and coronary artery disease. Intervention: Random assignment to medical therapy alone (602 patients) or medical therapy plus CABG (610 patients). Measurements: A battery of QOL instruments at baseline (98.9% complete) and 4, 12, 24, and 36 months after randomization (collection rates were 80% to 89% of those eligible). The principal prespecified QOL measure was the Kansas City Cardiomyopathy Questionnaire, which assesses the effect of heart failure on patients’ symptoms, physical function, social limitations, and QOL. Results: The Kansas City Cardiomyopathy Questionnaire overall summary score was consistently higher (more favorable) in the CABG group than in the medical therapy group by 4.4 points (95% CI, 1.8 to 7.0 points) at 4 months, 5.8 points (CI, 3.1 to 8.6 points) at 12 months, 4.1 points (CI, 1.2 to 7.1 points) at 24 months, and 3.2 points (CI, 0.2 to 6.3 points) at 36 months. Sensitivity analyses to account for the effect of mortality on follow-up QOL measurement were consistent with the primary findings. Limitation: Therapy was not masked. Conclusion: In this cohort of symptomatic high-risk patients with ischemic left ventricular dysfunction and multivessel coronary artery disease, CABG plus medical therapy produced clinically important improvements in quality of life compared with medical therapy alone over 36 months. [ABSTRACT FROM AUTHOR]

Background: The STICH Randomized Clinical Trial (Surgical Treatment for Ischemic Heart Failure) demonstrated that coronary artery bypass grafting (CABG) reduced all-cause mortality rates out to 10 years compared with medical therapy alone (MED) in patients with ischemic cardiomyopathy and reduced left ventricular function (ejection fraction ≤35%). We examined the economic implications of these results.Methods: We used a decision-analytic patient-level simulation model to estimate the lifetime costs and benefits of CABG and MED using patient-level resource use and clinical data collected in the STICH trial. Patient-level costs were calculated by applying externally derived US cost weights to resource use counts during trial follow-up. A 3% discount rate was applied to both future costs and benefits. The primary outcome was the incremental cost-effectiveness ratio assessed from the US health care sector perspective.Results: For the CABG arm, we estimated 6.53 quality-adjusted life-years (95% CI, 5.70-7.53) and a lifetime cost of $140 059 (95% CI, $106 401 to $180 992). For the MED arm, the corresponding estimates were 5.52 (95% CI, 5.06-6.09) quality-adjusted life-years and $74 894 lifetime cost (95% CI, $58 372 to $93 541). The incremental cost-effectiveness ratio for CABG compared with MED was $63 989 per quality-adjusted life-year gained. At a societal willingness-to-pay threshold of $100 000 per quality-adjusted life-year gained, CABG was found to be economically favorable compared with MED in 87% of microsimulations.Conclusions: In the STICH trial, in patients with ischemic cardiomyopathy and reduced left ventricular function, CABG was economically attractive relative to MED at current benchmarks for value in the United States.Registration: URL: https://www.Clinicaltrials: gov; Unique identifier: NCT00023595. [ABSTRACT FROM AUTHOR]

Objective: People living with HIV (PLWH) are at increased risk for cardiac dysfunction. It is unknown how their global longitudinal cardiac function, cardiac structure, and other indices of function progress over time. We aimed to characterize the longitudinal trend in cardiac structure and function in PLWH. Design: Retrospective study of PLWH with clinically obtained echocardiograms at an academic medical center. Methods: We reviewed archived transthoracic echocardiograms (TTEs) performed between 2001 and 2012 on PLWH. The primary outcome measures were progression of global longitudinal strain (GLS, left and right ventricles), LV mass, E/e′ ratio, LV end‐systolic, and ‐diastolic volumes using hierarchical mixed model analysis as a function of CD4+ T cell count and HIV RNA suppression. Models were adjusted for clinical and demographic characteristics. Results: We analyzed 469 TTEs from 150 individuals (median age 46 years, 58% male). Median CD4+ T cell counts at nadir and proximal to first echocardiogram were 85 and 222 cells/mm3, respectively. Over a median of 5 years, LV mass index increased regardless of nadir or proximal CD4+ T cell count or viral suppression status. PLWH with viral suppression at baseline had more normal GLS throughout the follow‐up period. There were no significant trends in LV end‐systolic volume index or E/e′. Conclusions: In PLWH, HIV viral suppression is associated with early gains in echocardiographic indices of cardiac function that persist for up to >5 years. HIV disease control impacts routine echocardiographic measures with known impacts on long‐term prognosis. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess the influence of enrolling site location and enrollment performance on the generalizability of STICH (Surgical Treatment for Ischemic Heart Failure) trial results. Background: The international STICH trial seeks to define the role of cardiac surgery for patients with ischemic cardiomyopathy. Methods: Baseline characteristics of 2,136 randomized STICH patients were entered into a multivariate equation created using the Duke Databank for Cardiovascular Diseases to predict their 5-year risk for death without cardiac surgery. Patients ordered by increasing predicted risk were assigned to 1 of 32 risk at randomization (RAR) groups created to share one-thirty-second of total predicted deaths. Numbers of patients sharing the same RAR group were compared between higher and lower enrolling site groupings and for countries tending to enroll high- or low-risk patients. Results: Country of enrollment was a stronger determinant of risk diversity than site enrollment performance among patients enrolled at 127 sites in 26 countries. Mean RAR differences among countries ranged from 9.4 (Singapore) to 18.6 (Germany). However, 1,614 of 2,136 patients (76%) from countries enrolling lower-risk patients shared the same RAR group with patients from countries enrolling higher-risk patients. Baseline characteristics responsible for risk differences of patients enrolled in the 2 country groupings were sufficiently similar to exert little influence on clinical decision making. Conclusions: STICH randomized patients are characterized by a continuous spectrum of risk, without discordant dominance from any site or country. Clinical site diversity promises to enhance the generalization of STICH trial results to a broad population of patients with ischemic cardiomyopathy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease; NCT00023595) [ABSTRACT FROM AUTHOR]

Platypnea-orthodeoxia syndrome is a rare disease defined by dyspnea and deoxygenation, induced by an upright position, and relieved by recumbency. Causes include shunting through a patent foramen ovale and pulmonary arteriovenous malformations. A 79-year-old woman experienced 2 syncopal episodes at rest and presented at another hospital. In the emergency department, she was hypoxic, needing 6 L/min of oxygen. Her chest radiograph showed nothing unusual. Transthoracic echocardiograms with saline microcavitation evaluation were mildly positive early after agitated-saline administration, suggesting intracardiac shunting. She was then transferred to our center. Right-sided heart catheterization revealed no oximetric evidence of intracardiac shunting while the patient was supine and had a low right atrial pressure. However, her oxygen saturation dropped to 78% when she sat up. Repeat transthoracic echocardiography while sitting revealed a dramatically positive early saline microcavitation-uptake into the left side of the heart. Transesophageal echocardiograms showed a patent foramen ovale, with right-to-left shunting highly dependent upon body position. The patient underwent successful percutaneous patent foramen ovale closure, and her oxygen supplementation was suspended. In patients with unexplained or transient hypoxemia in which a cardiac cause is suspected, it is important to evaluate shunting in both the recumbent and upright positions. In this syndrome, elevated right atrial pressure is not necessary for significant right-to-left shunting. Percutaneous closure, if feasible, is first-line therapy in these patients. [ABSTRACT FROM AUTHOR]

Concern has been raised about combining β blockers with angiotensin-receptor blockers in patients with heart failure. The VALsartan In Acute myocardial infarction (VALIANT) trial enrolled 14,703 patients with myocardial infarction complicated by heart failure or documented left ventricular systolic dysfunction. These patients were randomly allocated to treatment with valsartan, captopril, or both. Physicians were also encouraged to prescribe β blockers because of previous evidence of benefit. The baseline characteristics, treatments, and outcomes were compared among 4 groups: patients taking β blockers at admission only, at discharge only, at both admission and discharge, and neither. Patients treated with β blockers were at lower risk than those not treated at any period. Those treated with β blockers at both intervals had a lower 3-year mortality rate (17.7%) than those treated only at randomization (30.7%) or only at discharge (25.9%). The greatest mortality (35.1%) occurred in patients not treated at either point. No statistically significant interaction with prognosis was observed between β-blocker use and treatment with valsartan or valsartan plus captopril. Patients discharged with a β blocker had a significant survival advantage after adjustment for differences in baseline characteristics and intervening complications (hazard ratio 0.89, 95% confidence interval 0.81 to 0.98, p = 0.02). This association was most pronounced in patients prescribed consistent β blockers at randomization and discharge and was present in both patients with impaired and those with preserved systolic left ventricular function. These results have further confirmed that β blockers reduce the risk of death and nonfatal cardiovascular events in patients with heart failure or systolic left ventricular dysfunction after myocardial infarction. In conclusion, no evidence was found of adverse interactions between the angiotensin-receptor blocker valsartan and β blockers or of a negative effect of the combination of valsartan, captopril, and β blockers. [Copyright &y& Elsevier]

Left ventricular (LV) dyssynchrony is an increasingly important consideration in the evaluation and management of patients with LV systolic dysfunction. Improvements in clinical status, LV remodeling, and survival have been demonstrated with the use of cardiac resynchronization therapy (CRT). The current selection criteria for patients who undergo CRT include the presence of severe LV dysfunction, significant heart failure symptoms, and electrical dyssynchrony on surface electrocardiography (wide QRS interval). However, up to 40% of patients who undergo CRT do not experience reductions in symptoms or LV functional improvement. Because electrical dyssynchrony is not synonymous with contractile or mechanical dyssynchrony, efforts have been made to more accurately quantify mechanical dyssynchrony in the hope of improving the selection of patients for CRT. These efforts have focused largely on echocardiographic measures of mechanical dyssynchrony. A novel method to quantify LV mechanical dyssynchrony has been developed using phase analysis of gated single photon-emission computed tomographic myocardial perfusion imaging. In conclusion, this report describes potential advantages, compared with other methods, of using myocardial perfusion imaging to evaluate patients for CRT; reviews the method of the phase analysis technique to quantify dyssynchrony; reviews the available evidence of its utility; and describes future directions in research. [Copyright &y& Elsevier]

The development of heart failure and/or left ventricular systolic dysfunction (LVSD) in the setting of acute myocardial infarction (AMI) results in significant risk far above that of AMI independently. In patients admitted to the hospital for AMI, concomitant heart failure and/or LVSD on hospital admission or development of either or both of these conditions during admission are among the strongest predictors of inhospital death and are associated with significant increases in inhospital, 30-day, and long-term mortality and rehospitalization rates. Given the high risks in this population, aggressive treatment, comprising early initiation and sustained use of evidence-based treatments, is essential for improving prognosis. [Copyright &y& Elsevier]

Previous studies have shown that blacks have worse long-term outcomes than whites who have systolic heart failure. The reasons for these racial differences remain unclear. We investigated the effect of race and etiology of heart failure on outcomes of patients who had left ventricular (LV) systolic dysfunction. We studied records of 1,977 patients (27% black) who underwent cardiac catheterization who had New York Heart Association class II to IV symptoms and a LV ejection fraction <40%. Adjusted Cox’s proportional hazards regression models were examined for the end points of mortality, rehospitalization, and a composite of the 2. Black versus white patients were younger (median age 56 vs 63 years, p <0.01), more often were women (49% vs 33%, p <0.01), had diabetes (37% vs 31%, p = 0.02), and hypertension (75% vs 56%, p <0.01). Black patients were less likely to have significant coronary artery disease by angiography (41% vs 69%, p <0.01). Race was not an independent predictor of mortality (hazard ratio 1.09, 95% confidence interval 0.93 to 1.28, p = 0.27). After adjusted survival curves were stratified by race and etiology, the estimates indicated that among those patients who had nonischemic LV dysfunction, blacks appeared to have worse survival than whites. Thus, we found no racial differences in the long-term mortality risk of patients who had symptomatic LV systolic dysfunction. In conclusion, after stratifying by ischemic and nonischemic etiologies, we found decreased survival in blacks who had a nonischemic etiology compared with whites. There were no racial differences in rehospitalization between patients who had ischemic LV systolic dysfunction and those who did not. [Copyright &y& Elsevier]

Echocardiograms of 290 patients with dilated cardiomyopathy (ejection fraction ≤35%) were reviewed for the presence of left ventricular (LV) apical abnormalities; outcomes of stroke and death were then correlated with the presence of LV thrombus. During a follow-up of 31 months, 15 patients had a stroke or transient ischemic attack after the index echocardiogram (5.2%). Patients with LV thrombus on echocardiography had a significantly higher rate of stroke (adjusted odds ratio 3.4, p = 0.027) than those without echocardiographic evidence of thrombi. There was no difference in mortality between patients with and without thrombus (20.9% vs 21.1%, p = 0.726). [Copyright &y& Elsevier]