Development Of Symptomatic Heart Failure Research Articles

Left ventricular global systolic dysfunction has a significant role in the development of diastolic heart failure in patients with systemic hypertension

Regional left ventricular (LV) systolic dysfunction has been identified in diastolic heart failure (DHF). However, the relationship between regional or global LV systolic function and heart failure symptoms in DHF has not been evaluated in detail. The present study evaluates such relationships in patients with systemic hypertension (HT) and DHF. We assessed LV systolic and diastolic function in 220 consecutive patients with systemic HT and in 30 normal individuals (Control) using Doppler echocardiography. Patients with HT were assigned to groups with DHF, asymptomatic diastolic dysfunction (ADD) and no diastolic dysfunction (Simple HT). Ejection fraction in DHF was significantly decreased (63±8%) compared with the Control, Simple HT and ADD groups (67±5, 66±7 and 68±8%, respectively). Isovolumetric contraction time in DHF (70±30 msec) was significantly increased compared with those in the ADD, Simple HT and Control groups (31±17, 31±15 and 30±19 msec, respectively). Mitral annular systolic velocities were significantly decreased in the DHF and ADD groups (6.4±1.5 and 7.2±1.3 cm sec⁻¹, respectively) compared with those in the Simple HT and Control groups (8.5±1.8 and 8.4±3.0 cm sec⁻¹, respectively), and in the DHF group compared with the ADD group. LV global systolic dysfunction has a significant role in the development of heart failure symptoms associated with DHF in patients with systemic HT.

Section 5: Management of Asymptomatic Patients with Reduced Left Ventricular Ejection Fraction

Section 5: Management of Asymptomatic Patients with Reduced Left Ventricular Ejection Fraction

The prognostic value of circulating markers of collagen turnover after acute myocardial infarction

Background We assessed the time profiles and prognostic utility of circulating markers of collagen turnover (CTO) following acute myocardial infarction (MI). In contrast to previous studies, no patient had been pre-treated with inhibitors of the renin-angiotensin-aldosterone system (RAAS) at the time of initial assessment. Methods Plasma levels of N-terminal fragment of type I collagen (PINP), carboxy-terminal telopeptide of type I collagen (ICTP), N-terminal fragment of type III collagen (PIIINP), matrix metalloproteinase-1(MMP-1) and tissue inhibitor of MMPs type-1 (TIMP-1) were assessed in 233 patients following acute MI. The CTO markers were initially assessed prior to treatment by either captopril or losartan, at a median of 3 days following MI. In addition, blood samples were acquired at 1 month, 1 year and 2 years following MI. Development of heart failure symptoms, all-cause and cardiovascular death were recorded as endpoints during two years of follow-up. Results With the exception of PIIINP, all CTO markers demonstrated significant longitudinal changes following MI. At baseline, ICTP (p < 0.0001) and TIMP-1 (p = 0.01) levels were significantly elevated in patients who later died compared with survivors. In multivariable analysis only ICTP reached statistical significance as predictor of all cause death (p = 0.048). In patients developing symptoms of heart failure during follow-up, ICTP was the only significantly elevated CTO marker (p < 0.01). Conclusion The present study supports a prognostic role for ICTP in both the acute and chronic phase following MI.

Overlapping Phenotypes

Patient KM is a 26-year-old male in whom a systolic ejection murmur was recently identified on a routine physical examination. As part of his evaluation, he underwent 2-dimensional echocardiography, which revealed asymmetrical left ventricular (LV) hypertrophy with a maximum LV wall thickness of 22 mm in the basal anterior septum and extension of hypertrophy into the posterior septum. His LV ejection fraction was 55%, with a normal cavity size and no evidence of resting LV outflow tract obstruction. In addition, the myocardium was noted to be highly trabeculated from the apex to the midportion of the LV (Figure 1; online-only Data Supplement Movie I). The right ventricle was normal in size and function. He has never developed heart failure …

Transverse strain predicts exercise capacity in systemic right ventricle patients

Because transposition of great arteries (TGA) patients who underwent atrial switch repair (AS) remain asymptomatic for decades before development of symptomatic heart failure, there may be some clinical value to preclinical detection of ventricular dysfunction. Detection of systemic right ventricular (RV) dysfunction in patients who are asymptomatic may prompt early initiation of heart failure therapy and more frequent clinical follow-up. The objective of this study was to characterize longitudinal and transverse systolic function of the systemic RV using two-dimensional (2D) strain in patients with TGA after AS repair and to correlate these parameters with their exercise capacity. The study population consisted of 26 patients (20±6 years) with TGA after AS operation. Conventional echocardiography and bidimensional strain were performed on consecutive patients reporting to the out patient congenital heart disease clinic. Twenty-four healthy, age-matched individuals were used as control subjects. Analysis was performed on the non-systemic RVs of the control group. All the studied patients underwent treadmill exercise testing according to the Bruce II protocol. RV longitudinal 2D-strain in controls showed a base to apex gradient, while in patients was homogeneously reduced. Also RV transverse strain (i.e the radial deformation assessed by the apical 4 chamber view) showed a base to apex gradient in controls, while in patients was significantly increased in the mid and apical segments. In the systemic RV free wall, transverse strain was greater than longitudinal strain (p<0.0001), opposite from findings in the normal RV free wall (p: NS). Of interest, in AS-TGA patients we found a strong correlation between RV transverse 2D strain and exercise capacity (p<0.0001; R: 0.80). At multivariate analysis (including age, degree of tricuspid regurgitation, TAPSE, RV area fractional change, RV visually estimated ejection fraction, RV global longitudinal strain and RV global transverse strain) the best predictor of exercise capacity in AS-TGA patients was transverse 2D strain (p<0.0001). In AS-TGA patients there is a shift from a predominant longitudinal shortening to a predominant transverse thickening. The transverse thickening assessed by 2D transverse strain is correlated to exercise capacity of these patients. In the follow up of AS-TGA patients the monitoring of RV transverse myocardial deformation properties should be considered more than the simple evaluation of RV longitudinal function.

2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults

published online Mar 26, 2009; J. Am. Coll. Cardiol. Lynne Warner Stevenson, and Clyde W. Yancy Ganiats, Marvin A. Konstam, Donna M. Mancini, Peter S. Rahko, Marc A. Silver, Abraham, Donald E. Casey, Arthur M. Feldman, Gary S. Francis, Theodore G. Silver, Lynne Warner Stevenson, Clyde W. Yancy, Mariell Jessup, William T. Konstam, Donna M. Mancini, Keith Michl, John A. Oates, Peter S. Rahko, Marc A. M. Feldman, Gary S. Francis, Theodore G. Ganiats, Mariell Jessup, Marvin A. Transplantation, Sharon Ann Hunt, William T. Abraham, Marshall H. Chin, Arthur Force on Practice Guidelines, International Society for Heart and Lung American College of Cardiology Foundation/American Heart Association Task Diagnosis and Management of Heart Failure in Adults 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the This information is current as of March 27, 2009 http://content.onlinejacc.org/cgi/content/full/j.jacc.2008.11.013v1 located on the World Wide Web at: The online version of this article, along with updated information and services, is

Acute Ventricular-Arterial Coupling: Insights from an Elderly Hypertensive Canine Model

Advanced age and hypertension lead to increases in arterial (Ea) and ventricular (LV) systolic stiffness (ventricular-arterial (VA) coupling). Elderly persons with hypertensive heart disease develop heart failure symptoms during hypertensive episodes despite normal ejection fraction (HFnlEF). Elderly dogs with chronic renal hypertension display marked vascular and ventricular remodeling as well as increases in Ea and LV systolic (Ees) and diastolic (Ed) elastance and thus represent a model of those at risk for HFnlEF.

Cardiac Structure and Ventricular–Vascular Function in Persons With Heart Failure and Preserved Ejection Fraction From Olmsted County, Minnesota

Mechanisms purported to contribute to the pathophysiology of heart failure with normal ejection fraction (HFnlEF) include diastolic dysfunction, vascular and left ventricular systolic stiffening, and volume expansion. We characterized left ventricular volume, effective arterial elastance, left ventricular end-systolic elastance, and left ventricular diastolic elastance and relaxation noninvasively in consecutive HFnlEF patients and appropriate controls in the community. Olmsted County (Minn) residents without cardiovascular disease (n=617), with hypertension but no heart failure (n=719), or with HFnlEF (n=244) were prospectively enrolled. End-diastolic volume index was determined by echo Doppler. End-systolic elastance was determined using blood pressure, stroke volume, ejection fraction, timing intervals, and estimated normalized ventricular elastance at end diastole. Tissue Doppler e' velocity was used to estimate the time constant of relaxation. End-diastolic volume (EDV) and Doppler-derived end-diastolic pressure (EDP) were used to derive the diastolic curve fitting (alpha) and stiffness (beta) constants (EDP=alphaEDVbeta). Comparisons were adjusted for age, sex, and body size. HFnlEF patients had more severe renal dysfunction, yet smaller end-diastolic volume index and cardiac output and increased EDP compared with both hypertensive and healthy controls. Arterial elastance and ventricular end-systolic elastance were similarly increased in hypertensive controls and HFnlEF patients compared with healthy controls. In contrast, HFnlEF patients had more impaired relaxation and increased diastolic stiffness compared with either control group. From these cross-sectional observations, we speculate that the progression of diastolic dysfunction plays a key role in the development of heart failure symptoms in persons with hypertensive heart disease.

493: Re-transplantation for heart failure with preserved systolic function

Purpose: Re-transplantation has been considered for heart transplant patients with severe systolic dysfunction mainly due to underlying cardiac allograft vasculopathy (CAV) or severe rejection. However, some patients develop heart failure symptoms (shortness of breath, low cardiac output, fatigue, etc.) with preserved systolic function (defined as left ventricular ejection fraction (LVEF) >/= 40%). Similar to restrictive cardiomyopathic patients, these patients have symptoms refractory to medical therapy, which severely reduces their quality of life, necessitating re-transplantation.

Mitral Valve Cleft in Both Anterior and Posterior Leaflet: An Extremely Rare Anomaly

We herein report the case of a woman with clefts in the anterior and posterior mitral leaflets causing mitral insufficiency. The patient developed heart failure symptoms in the eighth decade of life and underwent mitral valve repair, with suture closure of both clefts. The reasons of its late presentation are discussed.

Section 5: Management of Asymptomatic Patients With Reduced Left Ventricular Ejection Fraction

Section 5: Management of Asymptomatic Patients With Reduced Left Ventricular Ejection Fraction

Myocardial T2* in Patients with Cardiac Failure Secondary to Iron Overload.

Introduction: Myocardial iron overload is a well established cause of heart failure in a number of haematological disorders and is the leading cause of death in β-thalassaemia major (TM). Once overt heart failure develops prognosis is very poor and it would therefore be desirable to identify patients at risk, prior to the development of symptomatic heart failure. Myocardial iron can now be rapidly and reproducibly assessed using a validated cardiac magnetic resonance (CMR) T2* technique. Left ventricular ejection fraction has been demonstrated to relate to myocardial T2* (normal >20ms), and accordingly iron overloaded patients with symptomatic heart failure are likely to have a low T2* but there are no reports of the myocardial T2* level in newly presenting patients with heart failure and the threshold for increased risk is also unknown.Purpose: To establish the distribution of myocardial T2* values in patients presenting with symptomatic heart failure secondary to iron overload.Methods: Database records of CMR T2* assessments over a 5 year period were reviewed to identify iron overloaded patients presenting with heart failure.Results: 28 patients (median age 29y, 11–79) with iron overload and documented heart failure were identified. 22 patients had thalassaemia major, 3 hereditary haemochromatosis, and 3 had miscellaneous transfusion dependent anaemias. The mean myocardial T2* in all groups was 6.8+/− 2.2ms reflecting severe iron loading by clinical criteria. See figure 1. Myocardial T2* values were similar between sub-groups as follows: TM patients 6.7+/− 2.4ms, haemochromatosis 7.7ms (6.7–7.4ms), miscellaneous 6.8ms (4.8–9.1ms).Conclusion: In this database review, the patients developing heart failure secondary to iron overload all had abnormal myocardial T2*, and overall 89% of heart failure patients had values less than 10ms, which reflects severe myocardial iron loading. This data suggests a myocardial T2* <10ms should be considered a threshold for risk of heart failure (with its attendant high mortality) and such patients should be treated aggressively with increased iron chelation. It also suggests that clinical heart failure occurs nearly exclusively in patients with severe myocardial iron loading. [Display omitted]

Relation of Lower Hematocrit to Progression from Asymptomatic Left Ventricular Dysfunction to Symptomatic Heart Failure (from the Studies of Left Ventricular Dysfunction Prevention Trial)

The relation between hematocrit and progression from asymptomatic left ventricular (LV) systolic dysfunction to symptomatic heart failure (HF) was examined in 2,821 patients from the Studies of Left Ventricular Dysfunction Prevention trial. Patients in the lowest hematocrit quartile (hematocrit < or = 40%) were at increased risk for the development of HF symptoms (hazard ratio [HR] 1.79, 95% confidence interval [CI] 1.37 to 2.34), first HF hospitalization (HR 2.35, 95% CI 1.52 to 3.62), and death or the development of HF symptoms (HR 1.60, 95% CI 1.28 to 1.99) compared with patients in the highest hematocrit quartile (hematocrit > 46%).

Approach to hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy is a genetic disease characterized by marked left ventricular (LV) hypertrophy. A dynamic LV outflow obstruction is present in approximately 20% of patients. Many affected individuals remain asymptomatic throughout life, others develop heart failure symptoms or atrial fibrillation (AF), and some die suddenly, often young and in the absence of previous symptoms. Stratification of sudden death risk is based on several markers, including a previous cardiac arrest, sustained ventricular tachycardia, family history of sudden death, extreme LV hypertrophy (>/= 30 mm), syncope, nonsustained ventricular tachycardia on Holter, and abnormal exercise blood pressure response. The implantable cardioverter-defibrillator is the most effective treatment for sudden death prevention, and should be considered in patients with either one strong or multiple risk factors. Important symptoms of heart failure develop in a minority of patients, largely as a consequence of diastolic dysfunction, and are usually treated with beta blockers, or verapamil. In patients with LV obstruction and severe symptoms unresponsive to medications, myectomy operation or alcohol septal ablation is indicated for relieving the gradient and improving quality of life. AF develops in approximately 20% of patients. Amiodarone is the most effective medication for preventing AF recurrences. In chronic AF, beta blockers or verapamil are usually effective for heart rate control. The threshold for anticoagulants is low, because even brief AF episodes have a substantial embolization risk.

Effects of diabetes mellitus and ischemic heart disease on the progression from asymptomatic left ventricular dysfunction to symptomatic heart failure: A retrospective analysis from the Studies of Left Ventricular Dysfunction (SOLVD) Prevention Trial

Background Emerging data suggest that diabetes mellitus is a risk factor for the progression of established heart failure only in those patients with ischemic cardiomyopathy. Whether diabetes mellitus is a risk factor for the progression from asymptomatic left ventricular systolic dysfunction to symptomatic heart failure in patients with left ventricular dysfunction of an ischemic cause is not known. Methods We performed a retrospective analysis of 2821 patients with asymptomatic left ventricular systolic dysfunction from the Studies of Left Ventricular Dysfunction (SOLVD) Prevention trial. We used adjusted survival analysis to examine the effects of ischemic heart disease and diabetes mellitus on 3 prespecified study end points: (1) development of heart failure (HF) symptoms, (2) HF hospitalization, and (3) death or development of symptoms. Results There is a statistically significant interaction between the cause of left ventricular systolic dysfunction and diabetes mellitus on the risk of development of heart failure symptoms ( P = .020). Patients with ischemic cardiomyopathy and diabetes had an increased risk of progression to symptomatic heart failure (HR = 1.56, P < .001), hospitalization for heart failure (HR = 2.16, P < .001), and death or development of symptoms (HR = 1.50, P < .001), compared with patients with ischemic cardiomyopathy without diabetes. In contrast, diabetes was not associated with an increased risk of reaching these end points in patients with nonischemic cardiomyopathy. Conclusions Diabetes mellitus is a risk factor for the progression from asymptomatic left ventricular systolic dysfunction to symptomatic heart failure, but this risk appears to be confined to those patients with ischemic cardiomyopathy.

Alcohol consumption and prognosis in patients with left ventricular systolic dysfunction after a myocardial infarction

ObjectivesWe assessed the influence of alcohol intake on the development of symptomatic heart failure (HF) in patients with left ventricular (LV) dysfunction after a myocardial infarction (MI). BackgroundIn contrast to protection from coronary heart disease, alcohol consumption has been linked to cardiodepressant effects and has been considered contraindicated in patients with HF. MethodsThe Survival And Ventricular Enlargement (SAVE) trial randomized 2,231 patients with a LV ejection fraction (EF) <40% following MI to an angiotensin-converting enzyme inhibitor or placebo. Patients were classified as nondrinkers, light-to-moderate drinkers (1 to 10 drinks/week), or heavy drinkers (>10 drinks/week) based on alcohol consumption reported at baseline. The primary outcome was hospitalization for HF or need for an open-label angiotensin-converting enzyme inhibitor. Analyses were repeated using alcohol consumption reported three months after MI. ResultsNondrinkers were older and had more comorbidities than light-to-moderate and heavy drinkers. In univariate analyses, baseline light-to-moderate alcohol intake was associated with a lower incidence of HF compared with nondrinkers (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.57 to 0.87), whereas heavy drinking was not (HR 0.91; 95% CI 0.67 to 1.23). After adjustment for baseline differences, light-to-moderate baseline alcohol consumption no longer significantly influenced the development of HF (light-to-moderate drinkers HR 0.93; 95% CI 0.75 to 1.17; heavy drinkers HR 1.25; 95% CI 0.91 to 1.72). Alcohol consumption reported three months after the MI similarly did not modify the risk of adverse outcome. ConclusionsIn patients with LV dysfunction after an MI, light-to-moderate alcohol intake either at baseline or following MI did not alter the risk for the development of HF requiring hospitalization or an open-label angiotensin-converting enzyme inhibitor.

Prevention and management of chronic heart failure in management of asymptomatic patients

Symptomatic heart failure is preceded by a somewhat prolonged asymptomatic stage in many patients. The number of patients with asymptomatic heart dysfunction is about 4-fold greater than the number of patients with clinically overt heart failure. Pharmacologic treatment with angiotensin-converting enzyme inhibitors and β-blockers (in particular carvedilol) of asymptomatic patients with systolic left ventricular (LV) dysfunction can prevent or delay the occurrence of symptoms and reduce mortality in the long term. Thus, it would be of utmost importance to recognize and appropriately treat these patients before they develop heart failure symptoms. The cost-effectiveness of screening for asymptomatic heart dysfunction in the general population and in cohorts at risk has not been extensively evaluated. A normal electrocardiogram has a high negative predictive value in patients at risk. Echocardiography is the best tool for diagnosis and characterization of heart dysfunction, but extensive use is limited by availability and cost. Natriuretic peptides (brain natriuretic peptide and N-terminal pro–brain natriuretic peptide) are very sensitive markers of heart dysfunction and volume overload, and their measurement has been proposed as a first-line test to select patients who need echocardiography. The definition of the etiology of LV dysfunction—in particular, of the ischemic etiology—has prognostic and therapeutic implications. In addition to revascularization, pharmacologic treatment with antiplatelets and statins is helpful in preventing new ischemic events and the development of heart failure. The prevention, or at least the delay, of clinical manifestations of heart failure is strongly related to an effective approach to the asymptomatic stage. Therefore, it is important to educate the entire medical community, particularly physicians in the primary care setting, about recognition and treatment of these patients.

Cardiac myocyte remodeling in hypertrophy and progression to failure

Contracting myocytes are highly variable in size and generally resemble elliptical cylinders in shape. Although their arrangement within the ventricular wall is rather complex, their length runs in a tangential manner, and their transverse axis runs transmurally. Consequently, it was proposed many years ago that changes in myocyte length (L) may contribute to chamber dilatation while myocyte transverse growth may be largely responsible for wall thickening during cardiac hypertrophy. In recent years, the development of more efficient, comprehensive, and precise methods of measuring cardiac myocyte dimensions has confirmed this. Specifically, pressure overloading during the compensated phase leads to concentric hypertrophy, which is characterized by an increase in myocyte cross-sectional area (CSA). Volume overloading during the compensated phase leads to a proportional increase in chamber diameter/wall thickness, which is characterized by increased L and CSA. Excessive myocyte lengthening (from series sarcomere addition) without a further change in CSA, appears to be the primary cellular alteration leading to chamber dilatation in the progression to failure. This event occurs long before the development of symptomatic heart failure. Understanding and targeting the associated abnormal signaling underlying this cellular change should have considerable clinical consequences.

Prevention of congestive heart failure by early, prehospital thrombolysis in acute myocardial infarction: a long-term follow-up study

The long term impact of pre-hospital thrombolysis in acute myocardial infarction on the subsequent development of heart failure symptoms was investigated in 362 consecutive patients. The pre hospital strategy, used in 61 patients, allowed for very early administration of streptokinase, within 1.2±0.6 (mean±S.D.) hours from pain onset. In contrast, 294 patients treated in hospital received lytic treatment within 2.0±0.9 hours. The pre hospital group showed faster reperfusion, as measured by the time to peak creatine kinase and to ST segment recovery, but only a slightly better ventricular function, as compared to hospital treated patients. Heart failure symptoms were significantly reduced in the pre hospital group during hospitalization and at long term follow up: there were less dyspnea, fatigue, orthopnea, nocturnal dyspnea, nocturia, peripheral edema and episodes of pulmonary edema. Angina was reduced as well. We conclude that the initial benefit of prehospital thrombolysis translates into long term reduction of heart failure symptoms, thus improving quality of life.

Diagnostic Value of B-Type Natriuretic Peptide Concentrations in Patients With Acute Myocardial Infarction

Although elevations of plasma atrial natriuretic peptide (ANP) concentrations have been shown to have prognostic significance in patients after acute myocardial infarction (AMI), the relation between plasma levels of B-type natriuretic peptide (BNP) and cardiovascular mortality remains unknown. To test the prognostic value of plasma ANP and BNP after AMI, plasma concentrations were measured a mean of 3 days after infarction in 75 patients. During a median follow-up of 19.7 months, 14 patients (18.4%) died of cardiovascular causes. On univariate analysis, plasma ANP and BNP, Killip class, modified Peel index, left ventricular ejection fraction, and presence of left ventricular failure were all associated with cardiovascular mortality. In contrast, plasma ANP was the only variable that correlated with the development of symptomatic heart failure and hospitalization. For the combined end point of cardiovascular mortality, symptomatic heart failure, and hospitalization, plasma neurohormones were the only variables of predictive value. By stepwise regression analysis, plasma BNP was the only significant independent predictor of cardiovascular mortality (p = 0.001), whereas plasma ANP identified patients at risk of symptomatic heart failure and hospitalization (p = 0.002 and 0.019, respectively). This study indicates that plasma BNP measured after AMI is a powerful neurohormonal predictor of subsequent cardiovascular mortality, whereas plasma ANP correlates better with the development of symptomatic heart failure and hospitalization. Routine measurement of both of these peptides in the period immediately after an AMI may provide a simple means of risk stratification with different information gained from each peptide. (Am J Cardiol 1996;78:284–287)