Search

Bariatric surgery may improve heart failure outcome in morbidly obese patients. However, the safety of bariatric surgery has not been investigated in morbidly obese patients hospitalized for heart failure. We evaluated the effects of bariatric surgery on parameters of hospitalization for heart failure in morbidly obese patients. We analyzed administrative discharge data of morbidly obese patients with heart failure as a primary diagnosis. Propensity score matching was performed to assess parameters of hospitalization in morbidly obese patients with and without a history of bariatric surgery. The discharges with diastolic heart failure codes were analyzed separately. Morbid obesity was coded in 4.4% of all discharges. Heart failure was the primary diagnosis in 6.0% of discharges with morbid obesity codes. Only 1% of discharges with morbid obesity and heart failure as primary diagnosis codes were coded for bariatric surgery. Length of stay (p

Introduction: Obesity may affect COVID-19 outcomes, independent of its association with hypertension, diabetes, chronic obstructive pulmonary disease and other cardiovascular disease. Hypothesis: Is obesity a major determinant of morbidity and mortality in patients with COVID-19? Methods: Retrospective analysis of all confirmed COVID-19 patients hospitalized at University Medical Center in New Orleans, Louisiana between February 1, 2020 to May 1, 2020 was performed. Intensive care unit (ICU) stay and fatal outcomes were analyzed as a function of body mass index (BMI), hypertension, diabetes, hyperlipidemia, and CKD. Risk factors for fatal outcomes were evaluated. Multivariate logistic regression was used to determine odds ratios. P-Value was set at 0.05. Results: From a sample size of 419 patients, 60(14.3%) were admitted to the ICU. Amongst ICU admits, 85% were African American (AA), 61.6% had BMI >30, 48.3% had diabetes, and 30% had chronic kidney disease. Mortality was 91.6% after ICU admission. Out of a total of 419, mortality was the highest in admits with BMI < 25(20.2%) and with BMI >40(20.3%). BMI > 40 was associated with a higher odds of death (Odds ratio: 3.9, 95% Confidence Interval (CI) 1.45-10.5) and ICU admission (OR:3.2 95% CI 1.1-9) after adjustment for age, race, sex and comorbidities. Conclusion: A direct association exists for BMI > 40 and in-hospital death, independent of comorbidities. Caution with aggressive intervention is warranted for such patients on presentation.

The mitochondria are mostly abundant in the heart, a beating organ of high- energy demands. Their function extends beyond being a power plant of the cell including redox balance, ion homeostasis and metabolism. They are dynamic organelles that are tethered to neighboring structures, especially the endoplasmic reticulum. Together, they constitute a functional unit implicated in complex physiological and pathophysiological processes. Their topology in the cell, the cardiac myocyte in particular, places them at the hub of signaling and calcium homeostasis, making them master regulators of cell survival or cell death. Perturbations in mitochondrial function play a central role in the pathophysiology of myocardial remodeling and progression of heart failure. In this minireview, we summarize important pathophysiological mechanisms, pertaining to mitochondrial morphology, dynamics and function, which take place in compensated hypertrophy and in progression to overt systolic heart failure. Published work in the last few years has expanded our understanding of these important mechanisms; a key prerequisite to identifying therapeutic strategies targeting mitochondrial dysfunction in heart failure.

The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention remains a controversial topic. The European Society of Cardiology and the American College of Cardiology/American Heart Association recommend at least 6 and 12 months of DAPT after PCI in patients with stable coronary artery disease or acute coronary syndrome, respectively. Although prolonging DAPT duration reduces ischemic events, it is associated with higher rates of bleeding and possible fatal outcomes. The DAPT score can be an important tool to identify patients who may still benefit from prolonged therapy. Nevertheless, several recent randomized controlled trials showed that shortening DAPT duration from 12 to 1–3 months reduces bleeding rates without significantly increasing ischemic event rates. These trials also suggested replacing acetylsalicylic acid (aspirin) with P2Y12 inhibitors after short-term DAPT. We review and compare past and present studies regarding DAPT and analyze the evidence favoring a short DAPT duration and the long-term single antiplatelet agent of choice.

Background/purpose Fractional flow reserve (FFR) remains underutilized due to practical concerns related to the need for hyperemic agents. These concerns have prompted the study of instantaneous wave-free ratio (iFR), a vasodilator-free index of coronary stenosis . Non-inferior cardiovascular outcomes have been demonstrated in two recent randomized clinic trials. We performed this meta-analysis to provide a necessary update of the diagnostic accuracy of iFR referenced to FFR based on the addition of eight more recent studies and 3727 more lesions. Methods We searched the PubMed, EMBASE, Central, ProQuest, and Web of Science databases for full text articles published through May 31, 2017 to identify studies addressing the diagnostic accuracy of iFR referenced to FFR ≤ 0.80. The following keywords were used: “instantaneous wave-free ratio” OR “iFR” AND “fractional flow reserve” OR “FFR.” Results In total, 16 studies comprising 5756 lesions were identified. Pooled diagnostic accuracy estimates of iFR versus FFR ≤ 0.80 were: sensitivity, 0.78 (95% CI, 0.76–0.79); specificity, 0.83 (0.81–0.84); positive likelihood ratio, 4.54 (3.85–5.35); negative likelihood ratio, 0.28 (0.24–0.32); diagnostic odds ratio, 17.38 (14.16–21.34); area under the summary receiver-operating characteristic curve, 0.87; and an overall diagnostic accuracy of 0.81 (0.78–0.84). Conclusions In conclusion, iFR showed excellent agreement with FFR as a resting index of coronary stenosis severity without the undesired effects and cost of hyperemic agents. When considering along with its clinical outcome data and ease of application, the diagnostic accuracy of iFR supports its use as a suitable alternative to FFR for physiology-guided revascularization of moderate coronary stenoses. Summary We performed a meta-analysis of the diagnostic accuracy of iFR referenced to FFR. iFR showed excellent agreement with FFR as a resting index of coronary stenosis severity without the undesired effects and cost of hyperemic agents. This supports its use as a suitable alternative to FFR for physiology-guided revascularization of moderate coronary stenoses.

INTRODUCTION Both resting and hyperemic physiologic methods to guide coronary revascularization improve cardiovascular outcomes compared with angiographic guidance alone. Fractional flow reserve (FFR) remains underutilized due to concerns regarding hyperemia, prompting study of resting distal to aortic coronary pressure (Pd/Pa). Pd/Pa is a vasodilator-free resting index unlike FFR. While Pd/Pa is similar to another resting index, instantaneous wave-free ratio (iFR), it is a whole-cycle measurement not limited to the wave-free diastolic period. Pd/Pa is not validated clinically although multiple accuracy studies have been performed. Our meta-analysis examines the overall diagnostic accuracy of Pd/Pa referenced to FFR, the accepted invasive standard of ischemia. METHODS We searched PubMed, EMBASE, Central, ProQuest, and Web of Science databases for full text articles published through August 9, 2017 addressing the diagnostic accuracy of Pd/Pa referenced to FFR

Obese patients with heart failure have a more favorable outcome than their normal weight counterparts. However, the safety of bariatric surgery in obese patients with heart failure due to left ventricular systolic dysfunction has been questioned. We utilized data from The National Inpatient Sample

Aims Volume overload and venous congestion are typically viewed as a consequence of advanced and of acute heart failure (HF) and renal failure (RF) although it is possible that hypervolaemia itself might be a critical intermediate in the pathophysiology of these diseases. This study aimed at elucidating whether peripheral venous congestion is sufficient to promote changes in inflammatory, neurohormonal, and endothelial phenotype similar to those observed in HF and RF. Methods To experimentally model peripheral venous congestion, we developed a new method (so-called venous stress test) and applied the methodology on 24 healthy subjects (14 men, age 35 ± 2 years). Venous arm pressure was increased to ∼30 mmHg above the baseline level by inflating a tourniquet cuff around the dominant arm (test arm). Blood and endothelial cells (ECs) were sampled from test and control arm (lacking an inflated cuff) before and after 75 min of venous congestion, using angiocatheters and endovascular wires. Magnetic beads coated with EC-specific antibodies were used for EC separation; amplified mRNA was analysed by Affymetrix HG-U133 Plus 2.0 Microarray. Results Plasma interleukin-6 (IL-6), endothelin-1 (ET-1), angiotensin II (AII), vascular cell adhesion molecule-1 (VCAM-1), and chemokine (C-X-C motif) ligand 2 (CXCL2) were significantly increased in the congested arm. A total of 3437 mRNA probe sets were differentially expressed ( P < 0.05) in venous ECs before vs. after testing, including ET-1, VCAM-1, and CXCL2. Conclusion Peripheral venous congestion causes release of inflammatory mediators, neurohormones, and activation of ECs. Overall, venous congestion mimicked, notable aspects of the phenotype typical of advanced and of acute HF and RF.

Angiotensin-converting enzyme (ACE) inhibition is clearly beneficial in patients with hypertension, heart failure, and post-myocardial infarction left ventricular (LV) dysfunction. However, whereas initial trials had reported a benefit of ACE inhibition in high-risk vascular patients, current trials of ACE inhibition have failed to demonstrate a clear benefit in vascular patients who are receiving risk-reduction interventions. The purpose of this review is to analyze the reasons behind the failure of the most recent trials of ACE inhibitors in vascular patients without overt LV dysfunction. The reader will gain an understanding of the time-dependent trend towards a reduction in the absolute benefit conferred by ACE inhibition in patients with vascular atherosclerosis as risk reduction interventions are increasingly implemented.Major trials with a follow-up period of at least 1 year assessing the use of ACE inhibitors in patients with a history of cardiac or vascular events were identified via a PubMed literature search. All-cause and cardiovascular mortality outcomes were reported for each trial, as well as the use of aspirin, lipid-lowering drugs and β-blockers, and the mean LV ejection fraction.The findings of recent trials do not support the use of ACE inhibitors in vascular patients who, adherent with risk reduction therapy, do not have hypertension, diabetes, or LV dysfunction.

The relative impact of comorbidities and parameters of left ventricular diastolic function on clinical outcome has not been thoroughly investigated in patients who are hospitalized for heart failure decompensation and found to have preserved ejection fraction. We identified 98 HFpEF patients among 1452 patients admitted with acute heart failure. Clinical characteristics, hemoglobin levels, estimated glomerular filtration rate (eGFR), B-type natriuretic peptide (BNP) and Doppler-echocardiographic parameters were analyzed. The primary end point of the study combined death and rehospitalization for decompensated heart failure after the index hospitalization. Mean age was 76 ± 9 years. LV ejection fraction, E/E (a) ratio, and estimated systolic pulmonary artery pressure were 61 (55-67)%, 12.9 (9.4-15.1), 40 (32-46) mmHg, respectively. BNP values, hemoglobin and eGFR were 287 (164-562) pg/mL, 11.3 (10.4-12.4) g/dL and 45 (37-74) mL/min/m(2), respectively. During a mean follow-up of 17 ± 11 months, 56% reached the primary endpoint of the study: 31 died and 24 were re-hospitalised for heart failure. Diabetes [HR = 1.76 (1.03-3.00), P = 0.039], lower systolic blood pressure [HR = 0.99 (0.97-0.99), P = 0.016], hemoglobin [HR = 0.62 (0.49-0.76), P < 0.0001], and eGFR [HR = 0.98 (0.97-0.99), P = 0.004] were associated with a poor outcome. Neither BNP nor echocardiographic parameters were correlated with outcome. Comorbidities primarily correlate with outcome in patients with HFpEF.

Cardiac cachexia occurs in severe heart failure (HF).1,2 Heart transplantation (HTx) is associated with weight gain and the frequent development of obesity. Although this weight gain has been attributed to glucocorticoid therapy, it is more dramatic than after other solid organ transplants, despite similar steroid regimens, and also unrelated to steroid dose,3 suggesting that other mechanisms are responsible. Leptin is an adipo(cyto)kine produced primarily by adipocytes that acts on the hypothalamus to decrease appetite and increases energy expenditure.4 Plasma leptin is thought to reflect adiposity, and obesity is associated with elevated leptin. Resistance to the appetite-suppressing effects of leptin is thought to co-exist with obesity and insulin resistance in the metabolic syndrome, but the mechanisms are poorly understood.

SummaryBackgroundLeft ventricular (LV) longitudinal deformation is a good marker of intrinsic myocardial dysfunction in pressure overload cardiomyopathies.AimTo assess the effect of valvuloarterial haemodynamic load on LV longitudinal deformation in patients with aortic valve stenosis (AVS) and preserved LV ejection fraction (LVEF).MethodsGlobal LV longitudinal strain (GLS) was measured using speckle tracking imaging in a series of 82 consecutive patients with AVS (mean age 75±10years; 50% men). The global (valvular+arterial) haemodynamic load imposed on the LV was estimated by the valvuloarterial impedance (Zva), and was calculated using either arm-cuff systolic peripheral blood pressure or systolic central aortic blood pressure estimated by SphygmoCor®.ResultsAmong this series of 82 patients with preserved LVEF, 79% had reduced LV GLS (

Takotsubo cardiomyopathy (TC) is often a diagnosis of exclusion. Biomarker profiles, including BNP/Troponin ratio, may assist in diagnosis in cases precluding early coronary angiography. A 64 year-old female presented with 2 weeks of severe abdominal pain. Her medical history included chronic

Aims Severe heart failure (HF) is often associated with cachexia that reverses post-heart transplantation (HTx) with frequent development of obesity. Ghrelin is a novel appetite-stimulating hormone. The aim was to determine the role of ghrelin in regulating appetite, food intake, and body composition in HF and post-HTx. Methods and results We measured serial ghrelin, hunger sensation, caloric intake, and body composition in 12 HF patients awaiting HTx, 12 patients 12.7 ± 8.6 months post-HTx, and 7 controls. Seven of 12 HF patients were followed for longitudinal analysis post-HTx. Body mass index was 23.1 ± 3.1 in HF and 31.5 ± 5.5 post-HTx (P < 0.001). Heart transplantation patients had gained 18.0 ± 7.7 kg since HTx. Ghrelin area under the curve between controlled meals (control: 186 ± 39; HF: 264 ± 71; HTx: 194 ± 47 ng min/mL, P < 0.007) was higher in HF, but test meal caloric intake (control: 1185 ± 650; HF: 391 ± 103; HTx: 831 ± 309 kcal, P < 0.008) was lower in HF. The longitudinal analysis confirmed these findings. Conclusion Heart failure may be associated with resistance to the appetite-stimulating effects of ghrelin, which may contribute to cachexia. Heart transplantation may be associated with resolution of ghrelin resistance, which may contribute to weight gain. These findings are preliminary and should be confirmed in larger trials.

Background The mechanisms that contribute to limit functional capacity are incompletely understood in patients with preserved resting ejection fraction (HFpREF). We assessed left ventricular (LV) systolic response to dynamic exercise in patients with HFpREF and in patients with similar comorbidities to HFpREF patients but without history or evidence of heart failure. Methods and Results Twenty-five HFpREF patients in steady-state clinical condition without significant coronary artery disease and 25 hypertensive controls underwent exercise echocardiography. At rest, systolic pulmonary artery pressure, left atrial area, E/A and E/e′ ratios were greater in patients with HFpREF than in control patients, whereas peak systolic mitral annular velocity was lower in HFpREF patients. The exercise-induced changes in LVEF, forward stroke volume, and cardiac output were significantly lower in HFpREF compared with control patients (–4 ± 8 vs. +6 ± 6 %, P = .001; –4 ± 9 vs. +10 ± 10 mL, P < .0001, and 1.6 ± 1.2 vs. 3.5 ± 1.8 L/min, P < .0001, respectively). Exercise-induced changes in effective arterial elastance significantly differed in HFpREF and control patients (0.5 ± 0.6 vs. –0.2 ± 0.5 mm Hg/mL, P < .0001). In addition, 7 of the 25 HFpREF patients developed functional mitral regurgitation during exercise and none in controls. Conclusions When compared with patients with similar comorbidities but without history or evidence of heart failure, patients with HFpREF experience greater arterial stiffening and thereby a deterioration of global LV systolic performance during dynamic exercise.

Background— Indirect evidence implicates endothelial dysfunction in the pathogenesis of vascular diseases associated with obstructive sleep apnea (OSA). We investigated directly whether dysfunction and inflammation occur in vivo in the vascular endothelium of patients with OSA. The effects of continuous positive airway pressure (CPAP) therapy on endothelial function and repair capacity were assessed. Methods and Results— Thirty-two patients with newly diagnosed OSA and 15 control subjects were studied. Proteins that regulate basal endothelial nitric oxide (NO) production (endothelial NO synthase [eNOS] and phosphorylated eNOS) and inflammation (cyclooxygenase-2 and inducible NOS) and markers of oxidative stress (nitrotyrosine) were quantified by immunofluorescence in freshly harvested venous endothelial cells before and after 4 weeks of CPAP therapy. Vascular reactivity was measured by flow-mediated dilation. Circulating endothelial progenitor cell levels were quantified to assess endothelial repair capacity. Baseline endothelial expression of eNOS and phosphorylated eNOS was reduced by 59% and 94%, respectively, in patients with OSA compared with control subjects. Expression of both nitrotyrosine and cyclooxygenase-2 was 5-fold greater in patients with OSA than in control subjects, whereas inducible NOS expression was 56% greater. Expression of eNOS and phosphorylated eNOS significantly increased, whereas expression of nitrotyrosine, cyclooxygenase-2, and inducible NOS significantly decreased in patients who adhered to CPAP ≥4 hours daily. Baseline flow-mediated dilation and endothelial progenitor cell levels were lower in patients than in control subjects, and both significantly increased in patients who adhered to CPAP ≥4 hours daily. Conclusions— OSA directly affects the vascular endothelium by promoting inflammation and oxidative stress while decreasing NO availability and repair capacity. Effective CPAP therapy is associated with the reversal of these alterations.

The prevalence of chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) increases substantially with age. The coexistence of COPD and CHF is common but often unrecognized in elderly patients. To avoid overlooking COPD in elderly patients with known CHF pulmonary function tests should be routinely obtained. Likewise, to avoid overlooking CHF in elderly patients with known COPD left ventricular (LV) function should be routinely assessed. Plasma brain natriuretic peptide levels are useful to differentiate COPD exacerbation from CHF decompensation in patients presenting with acute dyspnea. Aging exacerbates skeletal muscle alterations that occur in patients with CHF and COPD. Skeletal muscle metabolic alterations and atrophy and the resulting deterioration of functional capacity progress rapidly in elderly patients with COPD and CHF. Physical conditioning reverses rapidly progressing skeletal muscle metabolic alterations and atrophy and promotes independence and life quality in the elderly. Physical conditioning is clearly an essential component of the management of elderly patients with COPD and CHF. The pharmacological management of patients with coexistent COPD and CHF should focus on not depriving these patients from long-term beta adrenergic blockade. Long-term beta adrenergic blockade has been repeatedly shown to improve survival in elderly patients with CHF due to LV systolic dysfunction and, contrary to conventional belief, is well tolerated by patients with COPD.

Background: Patients with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) may develop pulmonary hypertension at rest and during exercise. The cardiac correlates of pulmonary hypertension have been ascertained in the resting state, but seldom during exercise in these patients. Aims: We sought to determine the cardiac correlates of exercise induced pulmonary hypertension in patients with LVSD by monitoring the estimated pulmonary artery systolic pressure (PASP) by continuous Doppler echocardiography during semirecumbent bicycle exercise. Methods: Eighty-five patients (mean age 57 ± 13 years, 75% male) with CHF due to LVSD (LV ejection fraction [EF]

Pump thrombosis occurs during destination therapy (DT) with HeartMate II, a continuous blood flow left ventricular assist device (St Jude, Pleasanton, CA, USA). With adherence to stringent post-operative and long-term anticoagulation a low incidence of pump thrombosis was initially reported during DT. The increased PT incidence during DT that was reported in early 2013 was attributed to lenient anticoagulation. A wide range of pump thrombosis incidence during DT is being reported since the return to stringent post-operative and long-term anticoagulation. We searched PubMed from January 2008 to February 2016 for reports of pump thrombosis during mechanical circulatory support with HeartMate II and focus on the incidence rate of pump thrombosis from DT approval by the Food and Drug Administration to present. Pump thrombosis which may have been initially underestimated continues to complicate DT with HeartMate II despite stringent post-operative and long-term anticoagulation.

Arginine vasopressin (AVP) plays a central role in the regulation of water and electrolyte balance. Dysregulation of AVP secretion, along with stimulation of AVP V2 receptors, is responsible for hyponatremia (serum sodium concentration

Background -Vascular nitric oxide (NO)-mediated vasodilation is reduced in the limb vasculature of patients with chronic heart failure. Depressed gene expression of vascular endothelial NO synthase has been reported in experimental models of heart failure.We sought to investigate endothelial NO synthase (eNOS) mRNA expression in the skeletal muscle vasculature of patients with chronic heart failure (CHF) and in controls. Methods and results -Transcript levels for eNOS were measured and normalized to von Willebrand factor gene expression level, in samples of skeletal muscle from patients with CHF (n = 20) and healthy subjects (n = 7). CHF was not associated with a decrease in eNOS expression. There was a trend towards an increased expression in NYHA class IV patients. Similar results were found when normalized to GAPDH mRNA levels. Conclusion - Vascular endothelial dysfunction that is observed in patients with severe heart failure does not appear to be related to a specific decrease in the expression of the gene encoding for endothelial NOS.

Stroke yearly produces about 6.7 million worldwide deaths as the second leading cause. Pharmacotherapy for hypertension, an independent stroke risk factor, significantly reduces incidence. Although prior meta-analyses demonstrate various antihypertensive classes are superior to placebo in reducing

Objectives We sought to compare the in-hospital mortality of patients with acute decompensated heart failure (ADHF) who were receiving parenteral treatment with one of four intravenous vasoactive medications. Background There are limited data regarding the effects of the choice of intravenous vasoactive medication on in-hospital mortality in patients hospitalized with ADHF. Methods This was a retrospective analysis of observational patient data from the Acute Decompensated Heart Failure National Registry (ADHERE), a multicenter registry designed to prospectively collect data on each episode of hospitalization for ADHF and its clinical outcomes. Data from the first 65,180 patient episodes (October 2001 to July 2003) were included in this analysis. Cases in which patients received nitroglycerin, nesiritide, milrinone, or dobutamine were identified and reviewed (n = 15,230). Risk factor and propensity score-adjusted odds ratios (ORs) for in-hospital mortality were calculated. Results Patients who received intravenous nitroglycerin or nesiritide had lower in-hospital mortality than those treated with dobutamine or milrinone. The risk factor and propensity score-adjusted ORs for nitroglycerin were 0.69 (95% confidence interval [CI] 0.53 to 0.89, p ≤ 0.005) and 0.46 (94% CI 0.37 to 0.57, p ≤ 0.005) compared with milrinone and dobutamine, respectively. The corresponding values for nesiritide compared with milrinone and dobutamine were 0.59 (95% CI 0.48 to 0.73, p ≤ 0.005) and 0.47 (95% CI 0.39 to 0.56, p ≤ 0.005), respectively. The adjusted OR for nesiritide compared with nitroglycerin was 0.94 (95% CI 0.77 to 1.16, p = 0.58). Conclusions Therapy with either a natriuretic peptide or vasodilator was associated with significantly lower in-hospital mortality than positive inotropic therapy in patients hospitalized with ADHF. The risk of in-hospital mortality was similar for nesiritide and nitroglycerin.

Diastolic heart failure accounts for up to 40% of patients with congestive heart failure (CHF), and is associated with a better prognosis as compared to patients with systolic dysfunction. Nevertheless, patients with diastolic dysfunction have a significantly higher mortality as compared to the normal population. Reduced heart rate variability (HRV), a marker of autonomic dysfunction, is associated with increased mortality in patients with systolic heart failure. We therefore sought to determine to what extent HRV is altered in a population of patients with diastolic heart failure. Twenty-four hour ambulatory (Holter) recordings were performed in 19 consecutive patients with diastolic heart failure, in 9 patients with systolic heart failure, as well as in 9 healthy volunteers (normal controls). Time and frequency domain HRV variables were obtained for all three groups of patients. Both Time and Frequency domain variables were found to be reduced in both heart failure groups compared to normal controls. When compared with each other, patients with diastolic function had relatively higher values of HRV variables, compared to those with systolic dysfunction (SDNN, Total power, ULF power, all P ≤ 0.05). Patients with diastolic dysfunction have reduced HRV, suggesting a disturbed sympathetic-parasympathetic balance. Nevertheless, values for HRV are not as profoundly reduced as in patients with systolic dysfunction. The relative preservation of sympathetic-parasympathetic balance may explain the better prognosis in this patient population. (PACE 2004; 27:299–303)

Aims The SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK (SHOCK) Trial showed no benefit of early revascularization in patients aged ≥75 years with acute myocardial infarction and cardiogenic shock. We examined the effect of age on treatment and outcomes of patients with cardiogenic shock in the SHOCK Trial Registry. Methods and results We compared clinical and treatment factors in patients in the SHOCK Trial Registry with shock due to pump failure aged

Endothelin‐1 (ET‐1) is a pivotal mediator of vasoconstriction and inflammation in congestive states such as heart failure (HF) and chronic kidney disease (CKD). Whether peripheral venous congestion (VC) increases plasma ET‐1 at pressures commonly seen in HF and CKD patients is unknown. We seek to characterize whether peripheral VC promotes time‐ and dose‐dependent increases in plasma ET‐1 and whether these changes are sustained after decongestion. We used a randomized, cross‐over design in 20 healthy subjects (age 30 ± 7 years). To experimentally model VC, venous pressure was increased to either 15 or 30 mmHg (randomized at first visit) above baseline by inflating a cuff around the subject9s dominant arm; the nondominant arm served as a noncongested control. We measured plasma ET‐1 at baseline, after 20, 60 and 120 min of VC, and finally at 180 min (60 min after cuff release and decongestion). Plasma ET‐1 progressively and significantly increased over 120 min in the congested arm relative to the control arm and to baseline values. This effect was dose‐dependent: ET‐1 increased by 45% and 100% at VC doses of 15 and 30 mmHg, respectively ( P 0.05), and declined after 60 min of decongestion though remaining significantly elevated compared to baseline. In summary, peripheral VC causes time‐ and dose‐dependent increases in plasma ET‐1. Of note, the lower dose of 15 mmHg (more clinically relevant to HF and CKD patients) was sufficient to raise ET‐1. These findings support the potentially contributory, not merely consequential, role of VC in the pathophysiology of HF and CKD.

Functional mitral regurgitation (FMR) occurs commonly in patients undergoing left ventricular (LV) remodeling. It is ubiquitous in patients referred to cardiac transplantation for LV systolic dysfunction and predicts a poor prognosis. The LV remodeling that is responsible for FMR is well understood and involves regional LV dysfunction Mitral annular dilatation is present in patients with idiopathic dilated cardiomyopathy but most often absent in patients with ischemic cardiomyopathy. Nonrandomized observations indicate that implantation of a mitral undersized flexible mitral ring reduces the amount of FMR, reverses LV remodeling, and improves symptoms in patients with end-stage cardiomyopathy and severe FMR. Whether a surgical procedure that does not correct the major LV alterations leading to FMR can have long-lasting effects on the amount of FMR and the reversal of LV remodeling remains to be demonstrated in randomized trials.

OBJECTIVES We sought to investigate the effect of angiotensin-converting enzyme (ACE) inhibition

Background —We determined the short-term hemodynamic and clinical effects of levosimendan, a novel calcium-sensitizing agent, in patients with decompensated heart failure. Methods and Results —One hundred forty-six patients with New York Heart Association functional class III or IV heart failure (mean left ventricular ejection fraction 21±1%) who had a pulmonary capillary wedge pressure ≥15 mm Hg and a cardiac index ≤2.5 L · min −1 · m −2 were enrolled in a multicenter, double-blind, placebo-controlled study and randomized 2:1 to intravenous infusion of levosimendan or placebo. Drug infusions were uptitrated over 4 hours from an initial infusion rate of 0.1 μg · kg −1 · min −1 to a maximum rate of 0.4 μg · kg −1 · min −1 and maintained at the maximal tolerated infusion rate for an additional 2 hours. Levosimendan caused dose-dependent increases in stroke volume and cardiac index beginning with the lowest infusion rate and achieving maximal increases in stroke volume and cardiac index of 28% and 39%, respectively. Heart rate increased modestly (8%) at the maximal infusion rate and was not increased at the 2 lowest infusion rates. Levosimendan caused dose-dependent decreases in pulmonary capillary wedge, right atrial, pulmonary arterial, and mean arterial pressures. Levosimendan appeared to improve dyspnea and fatigue, as assessed by the patient and physician, and was not associated with a significant increase in adverse events. Conclusions —Levosimendan caused rapid dose-dependent improvement in hemodynamic function in patients with decompensated heart failure. These hemodynamic effects appeared to be accompanied by symptom improvement and were not associated with a significant increase in the number of adverse events. Levosimendan may be of value in the short-term management of patients with decompensated heart failure.

OBJECTIVESThis SHOCK Study report seeks to provide an overview of patients with cardiogenic shock (CS) complicating acute myocardial infarction (MI) and the outcome with various treatments. The outcome of patients undergoing revascularization in the SHOCK Trial Registry and SHOCK Trial are compared.BACKGROUNDCardiogenic shock is the leading cause of death in patients hospitalized for acute MI. The randomized SHOCK Trial reported improved six-month survival with early revascularization.METHODSPatients with CS complicating acute MI who were not enrolled in the concurrent randomized trial were registered. Patient characteristics were recorded as were procedures and vital status at hospital discharge.RESULTSBetween April 1993 and August 1997, 1,190 patients with CS were registered and 232 were randomized in the SHOCK Trial. Predominant left ventricular failure (78.5%) was most common, with isolated right ventricular shock in 2.8%, severe mitral regurgitation in 6.9%, ventricular septal rupture in 3.9% and tamponade in 1.4%. In-hospital Registry mortality was 60%, with ventricular septal rupture associated with a significantly higher mortality (87.3%) than all other categories (p < 0.01). The risk profile and mortality were lower for Registry patients who were managed with thrombolytic therapy and/or intra-aortic balloon counterpulsation, coronary angiography, angioplasty and/or coronary artery bypass surgery. After adjusting for these differences, the extent to which survival was improved with early revascularization was similar to that observed in the randomized SHOCK Trial.CONCLUSIONSIn this prospective Registry the etiology of CS was a mechanical complication in 12%. The similarity of the beneficial treatment effect in patients undergoing early revascularization in the SHOCK Trial Registry and SHOCK Trial provides strong support for the generalizability of the SHOCK Trial results.

OBJECTIVES We sought to evaluate the frequency of pulmonary congestion and associated clinical and hemodynamic findings in patients with suspected cardiogenic shock (CS). BACKGROUND The prevalence of pulmonary congestion in the setting of CS is uncertain. METHODS The 571 SHOCK Trial Registry patients with predominant left ventricular failure (LVF) were divided into four groups: Group A = no pulmonary congestion/no hypoperfusion = 14 (3%), Group B = isolated pulmonary congestion = 32 (6%), Group C = isolated hypoperfusion = 158 (28%) and Group D = congestion with hypoperfusion = 367 (64%). Statistical comparisons between Group C and D only, with regard to patient demographics, hemodynamics, treatment and outcome, were made. RESULTS A significant proportion of patients with shock had no pulmonary congestion (Group C = 28%, 95% CI, 24% to 31%). Age and gender in this group were similar to Group D. Group C patients were less likely to have a prior MI (p = 0.028), congestive heart failure (p = 0.005) and renal insufficiency (p = 0.032), and the index MI was less likely to be anterior (p = 0.044). Cardiac output, cardiac index and ejection fraction were similar for the two groups but pulmonary capillary wedge pressure was slightly lower for Group C (22 vs. 24 mm Hg, p = 0.012). Treatment with thrombolysis, angioplasty and bypass surgery was similar in the two groups. In-hospital mortality rates for Groups C and D were 70% and 60%, respectively (p = 0.036). After adjustment, this difference was no longer statistically significant (p = 0.153). CONCLUSIONS Absence of pulmonary congestion at initial clinical evaluation does not exclude a diagnosis of CS due to predominant LVF and is not associated with a better prognosis.

OBJECTIVES This study was designed to evaluate the effects of low-dose enoximone on exercise capacity. BACKGROUND At higher doses the phosphodiesterase inhibitor, enoximone, has been shown to increase exercise capacity and decrease symptoms in heart failure patients but also to increase mortality. The effects of lower doses of enoximone on exercise capacity and adverse events have not been evaluated. METHODS This is a prospective, double-blind, placebo-controlled, multicenter trial (nine U.S. centers) conducted in 105 patients with New York Heart Association class II to III, ischemic or nonischemic chronic heart failure (CHF). Patients were randomized to placebo or enoximone at 25 or 50 mg orally three times a day. Treadmill maximal exercise testing was done at baseline and after 4, 8 and 12 weeks of treatment, using a modified Naughton protocol. Patients were also evaluated for changes in quality of life and for increased arrhythmias by Holter monitoring. RESULTS By the protocol-specified method of statistical analysis (the last observation carried-forward method), enoximone at 50 mg three times a day improved exercise capacity by 117 s at 12 weeks (p = 0.003). Enoximone at 25 mg three times a day also improved exercise capacity at 12 weeks by 115 s (p = 0.013). No increases in ventricular arrhythmias were noted. There were four deaths in the placebo group and 2 and 0 deaths in the enoximone 25 mg three times a day and enoximone 50 mg three times a day groups, respectively. Effects on degree of dyspnea and patient and physician assessments of clinical status favored the enoximone groups. CONCLUSIONS Twelve weeks of treatment with low-dose enoximone improves exercise capacity in patients with CHF, without increasing adverse events.

Background Intravenous infusion of nesiritide, a brain (B-type) natriuretic peptide, has beneficial hemodynamic effects in patients with decompensated congestive heart failure. We investigated the clinical use of nesiritide in such patients. Methods Patients hospitalized because of symptomatic congestive heart failure were enrolled in either an efficacy trial or a comparative trial. In the efficacy trial, which required the placement of a Swan–Ganz catheter, 127 patients with a pulmonary-capillary wedge pressure of 18 mm Hg or higher and a cardiac index of 2.7 liters per minute per square meter of body-surface area or less were randomly assigned to double-blind treatment with placebo or nesiritide (infused at a rate of 0.015 or 0.030 μg per kilogram of body weight per minute) for six hours. In the comparative trial, which did not require hemodynamic monitoring, 305 patients were randomly assigned to open-label therapy with standard agents or nesiritide for up to seven days. Results In the efficacy trial, ...

Background A preliminary study suggested that the long-acting late-generation calcium-channel blacker amlodipine has favorable effects on exercise tolerance and is safe to use in heart failure, in contrast to earlier generation agents. The goal of 2 multicenter studies was to assess the effect of adjunctive therapy with amlodipine in addition to standard therapy on exercise capacity, quality of life, left ventricular function, and safety parameters in patients with heart failure and left ventricular systolic dysfunction. Methods Two large multicenter trials examining the effects of amlodipine on these parameters over a 12-week period of therapy were undertaken in patients with mild to moderate heart failure and left ventricular systolic dysfunction. A total of 437 patients with stable heart failure were studied in a randomized, double-blind, placebo-controlled prospective design. Results Amlodipine at a dose of 10 mg/day in addition to standard therapy in such patients was associated with no significant difference in change in exercise tolerance on a Naughton protocol compared with placebo in each trial. Among all patients taking amlodipine, exercise time increased 53 ± 9 (SE) seconds; exercise time for those taking placebo increased 66 ± 9 seconds ( P = not significant). There were no significant differences in changes of quality of life parameters between amlodipine- and placebo-treated patients, and there were no significant differences in symptom scores or New York Heart Association classification between groups. Left ventricular function (measured as ejection fraction) improved 3.4% ± 0.5% in amlodipine-treated patients and 1.5% ± 0.5% in placebo-treated patients ( P = .007). There was no statistically significant excess of important adverse events (episodes of worsening heart failure in 10% amlodipine-treated vs 6.3% of placebo-treated patients) or differences in need for changes in background medication between groups. Conclusions The addition of 10 mg of amlodipine per day to standard therapy in patients with heart failure is associated with no significant improvement in exercise time compared with placebo therapy over a 12-week period, and there was no increased incidence of adverse events. These data suggest that the addition of amlodipine to standard therapy in heart failure will not result in additional efficacy per se beyond standard therapy.

Background The leading cause of death in patients hospitalized for acute myocardial infarction is cardiogenic shock. We conducted a randomized trial to evaluate early revascularization in patients with cardiogenic shock. Methods Patients with shock due to left ventricular failure complicating myocardial infarction were randomly assigned to emergency revascularization (152 patients) or initial medical stabilization (150 patients). Revascularization was accomplished by either coronary-artery bypass grafting or angioplasty. Intraaortic balloon counterpulsation was performed in 86 percent of the patients in both groups. The primary end point was mortality from all causes at 30 days. Six-month survival was a secondary end point. Results The mean (+/-SD) age of the patients was 66+/-10 years, 32 percent were women, and 55 percent had been transferred from other hospitals. The median time to the onset of shock was 5.6 hours after infarction, and most infarcts were anterior in location. Ninety-seven percent of the patients assigned to revascularization underwent early coronary angiography, and 87 percent underwent revascularization; only 2.7 percent of the patients assigned to medical therapy crossed over to early revascularization without clinical indication. Overall mortality at 30 days did not differ significantly between the revascularization and medical-therapy groups (46.7 percent and 56.0 percent, respectively; difference, -9.3 percent; 95 percent confidence interval for the difference, -20.5 to 1.9 percent; P = 0.11). Six-month mortality was lower in the revascularization group than in the medical-therapy group (50.3 percent vs. 63.1 percent, P=0.027). Conclusions In patients with cardiogenic shock, emergency revascularization did not significantly reduce overall mortality at 30 days. However, after six months there was a significant survival benefit. Early revascularization should be strongly considered for patients with acute myocardial infarction complicated by cardiogenic shock. (N Engl J Med 1999;341:625-34.) (C) 1999, Massachusetts Medical Society.

OBJECTIVES The goal of this study was to further define the role of nesiritide (human b-type natriuretic peptide) in the therapy of decompensated heart failure (HF) by assessing the hemodynamic effects of three doses (0.015, 0.03 and 0.06 μg/kg/min) administered by continuous intravenous (IV) infusion over 24 h as compared with placebo. BACKGROUND Previous studies have shown beneficial hemodynamic, neurohormonal and renal effects of bolus dose and 6-h infusion administration of nesiritide in HF patients. Longer term safety and efficacy have not been studied. METHODS This randomized, double-blind, placebo-controlled multicenter trial enrolled subjects with symptomatic HF and systolic dysfunction (left ventricular ejection fraction ≤35%). Central hemodynamics were assessed at baseline, during a 24-h IV infusion and for 4 h postinfusion. RESULTS One hundred three subjects with New York Heart Association class II (6%), III (61%) or IV (33%) HF were enrolled. Nesiritide produced significant reductions in pulmonary wedge pressure (27% to 39% decrease by 6 h), mean right atrial pressure and systemic vascular resistance, along with significant increases in cardiac index and stroke volume index, with no significant effect on heart rate. Beneficial effects were evident at 1 h and were sustained throughout the 24-h infusion. CONCLUSIONS The rapid and sustained beneficial hemodynamic effects of nesiritide observed in this study support its use as a first-line IV therapy for patients with symptomatic decompensated HF.

OBJECTIVES The purpose of this study was to determine the acute and chronic effects of cyclooxygenase inhibition with aspirin and thromboxane A2receptor blockade with ifetroban on the chronic vasodilating effects of enalapril in the skeletal muscle circulation of patients with heart failure. BACKGROUND Angiotensin-converting enzyme inhibition and antiplatelet therapy with aspirin independently reduce the risk for subsequent nonfatal coronary events in survivors of myocardial infarction. The safety of the combined administration of angiotensin-converting enzyme inhibitors and aspirin has been questioned due to their divergent effects on the vascular synthesis of vasodilating prostaglandins. METHODS Forearm blood flow (ml/min/100 ml) at rest and during rhythmic handgrip exercise and after transient arterial occlusion was determined by strain gauge plethysmography before and 4 h and six weeks after combined administration of enalapril with either aspirin, ifetroban or placebo in a multicenter, double-blind, randomized trial of 62 patients with mild to moderate heart failure. RESULTS Before randomization, forearm hemodynamics were similar in the three treatment groups except for increased resting forearm blood flow and decreased resting forearm vascular resistance in the aspirin group when compared with the placebo group. After combined administration of enalapril and study drug for 4 h and six weeks, changes from prerandomization values of mean arterial pressure, forearm blood flow and forearm vascular resistance at rest, during handgrip exercise and after transient arterial occlusion did not differ among the three treatment groups. CONCLUSIONS These findings demonstrate that the vasodilating effects of enalapril in the skeletal muscle circulation of patients with heart failure are not critically dependent on prostaglandin pathways.

Background —In patients with severe congestive heart failure (CHF), short-term administration of dobutamine exerts sustained clinical benefits that are partially mediated by a training-like effect on skeletal muscle. Recently, physical training has been shown to enhance endothelial function in the skeletal muscle vasculature by improving endothelial function. Whether the dobutamine-induced training effect is also associated with an improvement in endothelial function in the skeletal muscle vasculature is currently unknown. Methods and Results —Flow-mediated vasodilation in response to peak reactive hyperemia was evaluated in the forearms of 9 patients with severe CHF who were treated with dobutamine for 72 hours. Resting and peak hyperemic brachial artery blood flow and diameter (BABF [mL/min] and BAD [mm], respectively) were measured by 2-dimensional and Doppler ultrasonography at baseline, at 3 and 72 hours during dobutamine infusion, and at 2 and 4 weeks after discontinuation of dobutamine therapy. In addition, the brachial artery response to sublingual (SL) administration of nitroglycerin (NTG) was evaluated at baseline and at 2 and 4 weeks after discontinuation of dobutamine therapy. Ten patients with severe CHF who did not receive dobutamine served as control subjects. Resting BABF was significantly increased at 3 and 72 hours (391.2±31.8 and 366.8±31.0 mL/min, respectively, compared with 289.8±18.6 mL/min at baseline; P P P Conclusions —In patients with severe CHF, short-term administration of dobutamine for 72 hours selectively improves vascular endothelial function for ≥2 weeks.

Since the 1980s, cardiopulmonary exercise testing has been applied to patients with congestive heart failure (CHF) to objectively assess exercise capacity, to risk stratify patients, and to assess the response to therapeutic interventions.1 Subsequently, peak oxygen consumption (Vo2) was reported to be a reliable prognostic index and to be particularly useful for the timing of cardiac transplantation in patients with advanced CHF caused by left ventricular systolic dysfunction.2 As peak Vo2 is derived from the Fick equation and as most patients achieve comparable arterial-venous oxygen differences when they give maximal effort, peak Vo2 has provided a noninvasive marker for peak cardiac output response and thus cardiac reserve. However, peak Vo2 is affected not only by the cardiac output response to exercise as observed in healthy subjects but also by limited skeletal muscle mass and perfusion in patients with advanced CHF. Thus the usefulness of peak Vo2 to predict prognosis in patients with CHF also results from an objective quantification of the derangements that the failing heart causes in the periphery. Not unexpectedly, CHF patients with severe skeletal muscle wasting and low peak Vo2 have a worse prognosis than patients with little or no muscle wasting and moderately reduced peak Vo2. Numerous studies before and after the advent of β-blocker therapy have repeatedly demonstrated the effectiveness of peak Vo2 to predict outcome in patients with heart failure.3–5 The prognostic power of ancillary data collected during cardiopulmonary testing, such as Vo2 at anaerobic threshold, percentage predicted …

BACKGROUND: A pooled analysis in cardiogenic shock due to acute coronary syndromes is desirable to assess the effect of early revascularization (ERV) across all ages and a wide spectrum of disease severity. METHODS: Only two randomized controlled trials (RCT), i.e. SMASH and SHOCK, met the inclusion criteria and were combined for a pooled analysis using individual patient data (n = 348). RESULTS: SMASH patients (n = 54, 16%) had more severe disease than SHOCK patients (n = 294, 84%). After adjustment for age, anoxic brain damage, non-inferior myocardial infarction, prior coronary artery bypass graft surgery, renal failure, systolic blood pressure, and selection for coronary angiography, one-year mortality was similar (relative risk SHOCK versus SMASH 0.87, 95% CI: 0.61-1.25). Relative risk of one-year death for ERV versus initial medical stabilization was 0.82 (95% CI: 0.70-0.96). There was no significant difference in the treatment effect by age (≤75 years relative risk at one year 0.79, 95% CI: 0.63-0.99; > 75 years relative risk at one year 0.93, 95% CI: 0.56-1.53; interaction P = 0.10). CONCLUSIONS: Only two RCT have been published emphasizing the difficulty of enrolling critically ill patients. Despite large differences in shock severity, ERV benefit is similar across all ages and not significantly different for the elderly.

Background: Many patients remain markedly symptomatic despite optimal current therapy for heart failure. Beta-blockers have often been viewed as contraindicated in this group because of their potential adverse short-term effects on cardiac function. Methods and Results: One hundred thirty-one patients with severe congestive heart failure were enrolled into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had symptomatic, advanced heart failure while on standard triple therapy, as evidenced by a mean ejection fraction of 0.22, marked reduction in distance traveled in a 6-minute corridor walk test, and severe impairment in quality of life measured by the Minnesota Living With Heart Failure Questionnaire. After a 2-week, open-label test of 6.25 mg twice daily carvedilol, 105 patients were randomized (2:1) to receive either carvedilol (up to 25 mg twice daily, n = 70) or matching placebo (n = 35) for 6 months while background therapy with digoxin, diuretics, and an angiotensin-converting enzyme inhibitor remained constant. Ten patients (8%) did not complete the open-label period because of adverse events and 11.4% in both the carvedilol and placebo groups dropped out in the double-blind phase. The study was terminated early by the Data Safety and Monitoring Board and follow-up evaluation was therefore aborted before the projected number of patients and follow-up time was achieved. Quality of life, which was the primary endpoint, improved similarly in the carvedilol and placebo groups, whereas the global assessment by the physicians and the patient exhibited a better response to carvedilol (P < .05). Hospitalization and mortality rate were too low to evaluate a difference, and exercise time and New York Heart Association classification did not change significantly in response to the drug. Left ventricular ejection fraction rose significantly (+0.09) in the carvedilol group compared with the placebo group (+0.02, P = .004). Conclusion: The beta-blocker carvedilol can be safely employed in patients with severe heart failure. Improved left ventricular function with a trend for some improvement in symptoms combined with the experience with the drug in the larger population of less severe patients in this multicenter trial suggests that carvedilol may have a favorable long-term effect in heart failure of diverse severity.

Katz, Stuart D., Jeannette Yuen, Rachel Bijou, and Thierry H. LeJemtel. Training improves endothelium-dependent vasodilation in resistance vessels of patients with heart failure. J. Appl. Physiol. 82(5): 1488–1492, 1997.—The effects of physical training on endothelium-dependent vasodilation in skeletal muscle resistance vessels were investigated in patients with heart failure. Forearm blood flows (ml ⋅ min−1 ⋅ 100 ml−1) in response to brachial arterial administration of acetylcholine (5 × 10−5 and 5 × 10−4 M at 1 ml/min) and nitroglycerin (5 × 10−6 and 5 × 10−5 M at 1 ml/min) were determined by strain-gauge venous occlusion plethysmography before and after 8 wk of daily handgrip exercise in 12 patients with chronic heart failure. After 8 wk of daily handgrip exercise, the vasodilatory responses to acetylcholine significantly increased from pretraining values, i.e., 16.6 ± 2.0 vs. 8.6 ± 1.3 ml ⋅ min−1 ⋅ 100 ml−1( P < 0.05) and 27.5 ± 1.5 vs. 14.6 ± 1.7 ml ⋅ min−1 ⋅ 100 ml−1( P < 0.05), respect- ively, whereas the vasodilatory responses to nitroglycerin did not change. Handgrip exercise training appears to specifically enhance endothelium-dependent vasodilation in the forearm skeletal muscle circulation of patients with heart failure.

Objectives. The aims of the study were to 1) assess the effects of 12 weeks of exercise training at low work loads (i.e., corresponding to ≤50% of peak oxygen consumption [Vo2]) on peak Vo2and hyperemic calf blood flow in patients with severe congestive heart failure; and 2) evaluate left ventricular diastolic pressure and wall stress during exercise performed at work loads corresponding to ≤50% and 70% to 80% of peak Vo2.Background. Whether the benefits of exercise training can be achieved at work loads that result in lower left ventricular diastolic wall stress than those associated with conventional work loads is unknown in patients with severe congestive heart failure.Methods. Sixteen patients with severe congestive heart failure trained at low work loads for 1 h/day, four times a week, for 12 weeks. Peak Vo2and calf and forearm reactive hyperemia were measured before and during training. Nine of the 16 patients underwent right heart catheterization and echocardiography during bicycle exercise at low and conventional work loads (i.e., 50% and 70% to 80% of peak Vo2, respectively).Results. The increase in left ventricular diastolic wall stress was substantially lower during exercise at low work loads than during exercise at conventional work loads, (i.e., [mean ± SEM] 23.3 ± 7.4 vs. 69.6 ± 8.1 dynes/cm2(p < 0.001). After 6 and 12 weeks of training, peak Vo2increased from 11.5 ± 0.4 to 14.0 ± 0.5 and 15.0 ± 0.5 ml/kg per min, respectively (p < 0.0001 vs. baseline for both). Peak reactive hyperemia significantly increased in the calf but not in the forearm. The increases in peak Vo2and calf peak reactive hyperemia correlated closely (r = 0.61, p < 0.02).Conclusions. In patients with severe congestive heart failure, peak Vo2is enhanced by exercise training at work loads that result in smaller increases in left ventricular diastolic wall stress than those observed at conventional work loads.(J Am Coll Cardiol 1997;29:597–603)

We report the case of a 51-year-old woman who underwent mitral valve replacement for prolapse with severe regurgitation, depressed ejection fraction, and atrial fibrillation. Two weeks post-operatively, a transesophageal echocardiogram was performed for bacteremia. The patient was found incidentally to have a large free-floating ball thrombus in the left atrium. The patient was managed with anticoagulation because of the high-risk nature of repeat surgery. One month following diagnosis, the patient still had persistent thrombus in the left atrium seen on transthoracic echocardiography despite therapeutic anticoagulation. Free-floating ball thrombus is a rare and dramatic finding seen on echocardiography in patients with mitral valve disease.

Background Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials. Methods and Results We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fraction ≤0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n=145) or carvedilol (n=133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class ( P =.014) or by a global assessment of progress judged either by the patient ( P =.002) or by the physician ( P P P =.029). In contrast, carvedilol therapy had little effect on indirect measures of patient benefit, including changes in exercise tolerance or quality-of-life scores. The effects of the drug were similar in patients with ischemic heart disease or idiopathic dilated cardiomyopathy as the cause of heart failure. Conclusions These findings indicate that, in addition to its favorable effects on survival, carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and an ACE inhibitor. (Circulation. 1996;94:2793-2799.)

Techniques which are currently used to measure skeletal muscle blood flow (SMBF) in patients with congestive heart failure (CHF) are neither convenient nor accurate. They have led to discrepant results in patients with congestive heart failure and are, in part, responsible for the ongoing debate regarding the factors which limit the rise in body oxygen consumption during exercise in these patients. However, direct measurement of SMBF may not be needed during exercise in patients with severe CHF. Their skeletal muscles maximally extract oxygen. Consequently, increase in oxygen consumption by the skeletal muscles is only mediated by a concomitant increase in SMBF. In patients with severe CHF, peak body oxygen consumption attained during maximal exercise closely depends on the rise in SMBF, and thus provides an indirect measurement of SMBF.