Angiotensin-Neprilysin Inhibition and Renal Outcomes in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: In patients with heart failure, chronic kidney disease is common and associated with a higher risk of renal events than in patients without chronic kidney disease. We assessed the renal effects of angiotensin/neprilysin inhibition in patients who have heart failure with preserved ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction). METHODS: In this randomized, double-blind, event-driven trial, we assigned 4822 patients who had heart failure with preserved ejection fraction to receive sacubitril/valsartan (n=2419) or valsartan (n=2403). Herein, we present the results of the prespecified renal composite outcome (time to first occurrence of either: ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease, or death from renal causes), the individual components of this composite, and the influence of therapy on eGFR slope. RESULTS: At randomization, eGFR was 63±19 mL·min-1·1.73 m-2. At study closure, the composite renal outcome occurred in 33 patients (1.4%) assigned to sacubitril/valsartan and 64 patients (2.7%) assigned to valsartan (hazard ratio, 0.50 [95% CI, 0.33-0.77]; P=0.001). The treatment effect on the composite renal end point did not differ according to the baseline eGFR (<60 versus ≥60 mL·min-1·1.73 m-2 (P-interaction=0.92). The decline in eGFR was less for sacubitril/valsartan than for valsartan (-2.0 [95% CI, -2.2 to -1.9] versus -2.7 [95% CI, -2.8 to -2.5] mL·min-1·1.73 m-2 per year). CONCLUSIONS: In patients with heart failure with preserved ejection fraction, sacubitril/valsartan reduced the risk of renal events, and slowed decline in eGFR, in comparison with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

Baseline Characteristics of Patients With Heart Failure and Preserved Ejection Fraction in the PARAGON-HF Trial.

BACKGROUND: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. METHODS AND RESULTS: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), ß-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease. CONCLUSIONS: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.

Shortness of breath in clinical practice: A case for left atrial function and exercise stress testing for a comprehensive diastolic heart failure workup.

The symptom cluster of shortness of breath (SOB) contributes significantly to the outpatient workload of cardiology services. The workup of these patients includes blood chemistry and biomarkers, imaging and functional testing of the heart and lungs. A diagnosis of diastolic heart failure is inferred through the exclusion of systolic abnormalities, a normal pulmonary function test and normal hemoglobin, coupled with diastolic abnormalities on echocardiography. Differentiating confounders such as obesity or deconditioning in a patient with diastolic abnormalities is difficult. While the most recent guidelines provide more avenues for diagnosis, such as incorporating the left atrial size, little emphasis is given to understanding left atrial function, which contributes to at least 25% of diastolic left ventricular filling; additionally, exercise stress testing to elicit symptoms and test the dynamics of diastolic parameters, especially when access to the "gold standard" invasive tests is lacking, presents clinical translational gaps. It is thus important in diastolic heart failure work up to understand left atrial mechanics and the role of exercise testing to build a comprehensive argument for the diagnosis of diastolic heart failure in a patient presenting with SOB.

Giant coronary aneurysm presenting as a cardiac mass on transthoracic echocardiogram.

A 69-year-old man with a history of ischaemic heart disease and previous stent implantation in the right coronary artery (RCA) was found to have a large well-encapsulated mass attached to the right atrium on a routine transthoracic echocardiogram. Subsequent investigations including transoesophageal echocardiography and CT coronary angiogram suggested an RCA aneurysm formation in relation to the prior stented segment, further confirming on coronary angiogram a large ectatic vessel with a giant aneurysm measuring 2.4×2.7 cm. Giant coronary artery aneurysms are rare and here we present interesting images of a case initially picked up on transthoracic echocardiography.

Therapeutic interventions for heart failure with preserved ejection fraction: A summary of current evidence.

Heart failure with preserved ejection fraction (HFPEF) is common and represents a major challenge in cardiovascular medicine. Most of the current treatment of HFPEF is based on morbidity benefits and symptom reduction. Various pharmacological interventions available for heart failure with reduced ejection fraction have not been supported by clinical studies for HFPEF. Addressing the specific aetiology and aggressive risk factor modification remain the mainstay in the treatment of HFPEF. We present a brief overview of the currently recommended therapeutic options with available evidence.

Comorbid Heart Failure and Renal Impairment: Epidemiology and Management.

Heart failure mortality is significantly increased in patients with baseline renal impairment and those with underlying heart failure who subsequently develop renal dysfunction. This accelerated progression occurs independent of the cause or grade of renal dysfunction and baseline risk factors. Recent large prospective databases have highlighted the depth of the current problem, while longitudinal population studies support an increasing disease burden. We have extensively reviewed the epidemiological and therapeutic data among these patients. The evidence points to a progression of heart failure early in renal impairment, even in the albuminuric stage. The data also support poor prescription of prognostic therapies. As renal function is the most important prognostic factor in heart failure, it is important to establish the current understanding of the disease burden and the therapeutic implications.

The cardiorenal syndrome.

The term 'cardiorenal syndrome' (CRS) has increasingly been used in recent years without a constant meaning and a well-accepted definition. To include the vast array of interrelated derangements, and to stress the bidirectional nature of the heart-kidney interactions, the classification of the CRS today includes 5 subtypes whose etymology reflects the primary and secondary pathology, the time frame and simultaneous cardiac and renal codysfunction secondary to systemic disease. The CRS can generally be defined as a pathophysiological disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Type I CRS reflects an abrupt worsening of cardiac function (e.g. acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type II CRS describes chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and permanent chronic kidney disease. Type III CRS consists in an abrupt worsening of renal function (e.g. acute kidney ischemia or glomerulonephritis) causing acute cardiac disorder (e.g. heart failure, arrhythmia, ischemia). Type IV CRS describes a state of chronic kidney disease (e.g. chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy and/or increased risk of adverse cardiovascular events. Type V CRS reflects a systemic condition (e.g. diabetes mellitus, sepsis) causing both cardiac and renal dysfunction. Biomarkers can help to characterize the subtypes of the CRS and to indicate treatment initiation and effectiveness. The identification of patients and the pathophysiological mechanisms underlying each syndrome subtype will help to understand clinical derangements, to make the rationale for management strategies and to design future clinical trials with accurate selection and stratification of the studied population.

Cardiorenal syndrome.

The term cardiorenal syndrome (CRS) increasingly has been used without a consistent or well-accepted definition. To include the vast array of interrelated derangements, and to stress the bidirectional nature of heart-kidney interactions, we present a new classification of the CRS with 5 subtypes that reflect the pathophysiology, the time-frame, and the nature of concomitant cardiac and renal dysfunction. CRS can be generally defined as a pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction of 1 organ may induce acute or chronic dysfunction of the other. Type 1 CRS reflects an abrupt worsening of cardiac function (e.g., acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type 2 CRS comprises chronic abnormalities in cardiac function (e.g., chronic congestive heart failure) causing progressive chronic kidney disease. Type 3 CRS consists of an abrupt worsening of renal function (e.g., acute kidney ischemia or glomerulonephritis) causing acute cardiac dysfunction (e.g., heart failure, arrhythmia, ischemia). Type 4 CRS describes a state of chronic kidney disease (e.g., chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy, and/or increased risk of adverse cardiovascular events. Type 5 CRS reflects a systemic condition (e.g., sepsis) causing both cardiac and renal dysfunction. Biomarkers can contribute to an early diagnosis of CRS and to a timely therapeutic intervention. The use of this classification can help physicians characterize groups of patients, provides the rationale for specific management strategies, and allows the design of future clinical trials with more accurate selection and stratification of the population under investigation.

Comparison of renal function and cardiovascular risk following acute myocardial infarction in patients with and without diabetes mellitus.

Renal dysfunction is an independent risk factor for cardiovascular (cv) disease and its associated complications. Diabetes mellitus (dm) is a common cause of renal dysfunction. Whether the presence or absence of dm modifies the relation between renal dysfunction and cv disease is unclear. The valiant trial identified 14,527 patients with acute myocardial infarction complicated by either clinical or radiologic signs of heart failure and/or left ventricular dysfunction for whom baseline creatinine was measured. Patients were randomly assigned to receive captopril, valsartan, or both. Glomerular filtration rate (gfr) was estimated using the 4-component modification of diet in renal disease equation. Using multivariable cox proportional modeling, the relation of overall mortality and composite cardiovascular events with estimated gfr (egfr) between patients with and without dm was compared. Mean egfrs were 66.8 +/- 22.0 and 71.2 +/- 21.0 ml/min/1.73 m2 for patients with (n = 3,358) and without dm (n = 11,169), respectively. The likelihood of experiencing death or the composite end point was higher in patients with than without dm for each level of renal function. the augmentation in risk of cv events based on reduced renal function was similar between groups. Each decrease in egfr by 10 units was associated with hazards of 1.09 (95% confidence interval 1.06 to 1.12, p <0.001) in patients with dm and 1.08 (95% confidence interval 1.06 to 1.10, p <0.001) in patients without dm for risk of fatal and nonfatal cv outcomes independent of treatment assignment. In conclusion, although dm is associated with higher risk of renal dysfunction and adverse cv outcomes, patients without dm had a relation between renal function and cv risk similar to that for patients with dm after high-risk acute myocardial infarction.

Usefulness of right ventricular fractional area change to predict death, heart failure, and stroke following myocardial infarction (from the VALIANT ECHO Study).

Severe right ventricular dysfunction independent of left ventricular ejection fraction increased the risk of heart failure (HF) and death after myocardial infarction (MI). The association between right ventricular function and other clinical outcomes after MI was less clear. Two-dimensional echocardiograms were obtained in 605 patients with left ventricular dysfunction and/or clinical/radiologic evidence of HF from the VALIANT echocardiographic substudy (mean 5.0 +/- 2.5 days after MI). Clinical outcomes included all-cause mortality, cardiovascular (CV) death, sudden death, HF, and stroke. Baseline right ventricular function was measured in 522 patients using right ventricular fractional area change (RVFAC) and was related to clinical outcomes. Mean RVFAC was 41.9 +/- 4.3% (range 19.2% to 53.1%). The incidence of clinical events increased with decreasing RVFAC. After adjusting for 11 covariates, including age, ejection fraction, and Killip's classification, decreased RVFAC was independently associated with increased risk of all-cause mortality (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.31 to 1.98), CV death (HR 1.62, 95% CI 1.30 to 2.01), sudden death (HR 1.79, 95% CI 1.26 to 2.54), HF (HR 1.48, 95% CI 1.17 to 1.86), and stroke (HR 2.95, 95% CI 1.76 to 4.95), but not recurrent MI. Each 5% decrease in baseline RVFAC was associated with a 1.53 (95% CI 1.24 to 1.88) increased risk of fatal and nonfatal CV outcomes. In conclusion, decreased right ventricular systolic function is a major risk factor for death, sudden death, HF, and stroke after MI.

The relationship between renal function and cardiac structure, function, and prognosis after myocardial infarction: the VALIANT Echo Study.

OBJECTIVES: The purpose of this study was to determine whether alterations in cardiac structure or function contribute to the increased risk associated with renal impairment after myocardial infarction (MI). BACKGROUND: Renal impairment is associated with adverse cardiovascular outcomes after MI. METHODS: Echocardiography was performed on 603 patients with left ventricular (LV) dysfunction, heart failure (HF), or both after MI. Patients were grouped according to their estimated glomerular filtration rate (eGFR), and measures of cardiac structure and function were related to baseline eGFR. The relationship between eGFR and cardiac structure and function and clinical outcomes of death or HF was assessed with multivariable Cox regression. RESULTS: Ejection fraction, infarct segment length, right ventricular function, and mitral deceleration time were not influenced by renal function. Patients with reduced eGFR had smaller LV and larger left atrial (LA) volumes and higher left ventricular mass index (LVMI) and LV mass/LV volume ratio. A greater proportion of the patients with reduced eGFR had LV hypertrophy. The relationship between eGFR and the outcome of death or HF was attenuated by including baseline differences in LVMI, and both LVMI and LA volume conferred additional prognostic information in a multivariable model. CONCLUSIONS: Renal impairment was associated with smaller LV and larger LA volumes and increased LVMI. Systolic function was similar when compared with patients with normal renal function. Thus, reduced systolic function cannot account for worse outcomes in patients with renal impairment after MI. Indirect measures of diastolic function suggest that diastolic dysfunction might be an important mediator of increased risk in this population.

Two-dimensional assessment of right ventricular function: an echocardiographic-MRI correlative study.

BACKGROUND: While echocardiography is used most frequently to assess right ventricular (RV) function in clinical practice, echocardiography is limited in its ability to provide an accurate measure of RV ejection fraction (RVEF). Hence, quantitative estimation of RV function has proven difficult in clinical practice. OBJECTIVE: We sought to determine which commonly used echocardiographic measures of RV function were most accurate in comparison with an MRI-derived estimate of RVEF. METHODS: We analyzed RV function in 36 patients who had cardiac MRI studies and echocardiograms within a 24 hour period. 2D parameters of RV function-right ventricular fractional area change (RVFAC), tricuspid annular motion (TAM), and transverse fractional shortening (TFS) were obtained from the four-chamber view. RV volumes and EFs were derived from volumetric reconstruction based on endocardial tracing of the RV chamber from the short axis images. Echocardiographic assessment of RV function was correlated with MRI findings. RESULTS: RVFAC measured by echocardiography correlated best with MRI-derived RVEF (r = 0.80, P < 0.001). Neither TAM (r = 0.17; P = 0.30) nor TFC (r = 0.12; p< 0.38) were significantly correlated with RVEF. CONCLUSIONS: RVFAC is the best of commonly utilized echocardiographic 2D measure of RV function and correlated best with MRI-derived RV ejection fraction. CONDENSED ABSTRACT: While echocardiography is used most frequently to assess RV function in clinical practice, echocardiography is limited in its ability to provide an accurate measure of RV ejection fraction (RVEF). Using cardiac MRI, RV fractional area change (RVFAC), determined either by MRI or echocardiography, was found to correlate best with MRI-derived RVEF.

Impact of prior antiplatelet therapy on risk of embolism in infective endocarditis.

BACKGROUND: Embolism is a dreaded complication of infective endocarditis (IE). Currently, antimicrobial therapy is the only medical intervention proven to decrease the risk of embolism associated with IE. We hypothesized that, because platelet aggregation is operative in the pathogenesis of vegetation formation, embolism associated with IE should occur less frequently among patients who have received prior, continuous daily antiplatelet therapy for noninfectious reasons. METHODS: We studied a retrospective cohort of adult patients with a diagnosis of IE who presented to the Mayo Clinic (Rochester, MN) during 1980-1998. The cohort was divided into 2 groups on the basis of whether they had received continuous daily antiplatelet therapy for at least 6 months prior to the time of hospitalization for IE. Antiplatelet therapy included aspirin, dipyridamole, clopidogrel, ticlopidine, or any of combination of these agents. The primary end point was a symptomatic embolic event that occurred prior to or during hospitalization. Multivariable logistic regression was used to assess the impact of continuous daily antiplatelet therapy on risk of symptomatic emboli associated with IE. RESULTS: One hundred forty-seven (24.5%) of 600 patients experienced a symptomatic embolic event; the most common embolic manifestation was stroke (in 48.2% of patients). Embolic events occurred significantly less often among those who had received prior, continuous daily antiplatelet therapy (12.0% of patients who had received therapy vs. 27.8% patients who had not receive therapy; P<.001). After adjustment for several covariates known to influence both risk of embolism and propensity for antiplatelet use, the adjusted odds ratio for a symptomatic embolic event was 0.36 (95% confidence interval, 0.19-0.68; P=.002) for patients receiving continuous daily antiplatelet therapy. CONCLUSIONS: The risk of symptomatic emboli associated with IE was reduced in patients who received continuous daily antiplatelet therapy before onset of IE.

Comparison of regional versus global assessment of left ventricular function in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction: the valsartan in acute myocardial infarction echocardiographic study.

BACKGROUND: Left ventricular (LV) ejection fraction (EF) and wall-motion index (WMI) have both been shown to be independent predictors of outcome after myocardial infarction (MI). OBJECTIVES: We sought to determine whether these two measurements of LV systolic function provide similar or complementary information about prognosis after MI. METHODS: Echocardiography was performed in 610 patients with LV dysfunction, heart failure, or both after MI enrolled in the Valsartan in Acute MI trial. LVEF was estimated by biplane Simpson's rule, and WMI was assessed using a 16-segment model in 502 patients with echocardiograms of sufficient quality for wall-motion assessment. RESULTS: Both LVEF and WMI were independent predictors of adverse outcome after MI. LVEF conferred no additional prognostic information in multivariable analysis including WMI (P = .39) or number of affected segments (P = .53), whereas WMI (P = .02) and total number of affected segments (P = .006) remained significant even when adjusting for LVEF. CONCLUSIONS: Assessment of regional dysfunction by WMI or the number of affected segments has slightly more prognostic value than LVEF in patients with LV dysfunction, heart failure, or both after MI. Regional assessment might be a more sensitive predictor of outcome than global assessment in patients with acute MI.

Characterization of microvascular dysfunction after acute myocardial infarction by cardiovascular magnetic resonance first-pass perfusion and late gadolinium enhancement imaging.

PURPOSE: While both first-pass perfusion and late gadolinium enhancement by cardiovascular magnetic resonance (CMR) can assess coronary microvascular status in acute myocardial infarction (AMI), there are only limited data on their respective diagnostic utility. We aim to evaluate: the utility of first-pass perfusion and late gadolinium enhancement imaging in the detection and quantification of microvascular dysfunction after reperfused acute myocardial infarction, using TIMI frame count (TIMI FC) as the reference standard of microvascular assessment; and their relationship with infarct size and ventricular function. METHODS: First-pass perfusion and late gadolinium enhancement imaging were performed in 25 consecutive AMI patients (84% men, age 58 +/- 10) within 72 h of successful reperfusion. We assessed the myocardial extent of microvascular dysfunction using the size of the perfusion defect on first-pass perfusion (PD%) and the hypoenhanced core region within late gadolinium enhancement (MDEcore%). PD%, MDEcore%, and TIMI FC were analyzed independently of each other and with blinding to clinical data. We adjusted PD% and MDEcore% to the myocardial mass subtended by the infarct-related artery according to the 16-segment model. RESULTS: Median infarct size involved 13.9% (interquartile range: 8.5 to 22.2%) of the left ventricle and median left ventricular ejection fraction was 52% (interquartile range: 43 to 61%). PD% demonstrated evidence of microvascular dysfunction more frequently (84% vs. 36% of patients, p < 0.002) and involved a larger myocardial extent (23.5 +/- 17.5% vs. 3.5 +/- 7.7%, p < 0.001) compared to MDEcore%. PD% had strong correlations with TIMI FC (Spearman rho = 0.62, p < 0.001) and infarct size (rho = 0.64, p < 0.001), and a moderate correlation with LVEF (rho = -0.39, p = 0.055). MDEcore% also correlated with TIMI FC (rho = 0.54, p = 0.005) and infarct size (rho = 0.52, p < 0.01) but not with LVEF (p = NS). CONCLUSIONS: PD% appeared to provide a stronger noninvasive assessment of the microvascular function than MDEcore% and correlated well with prognostic markers such as left ventricular ejection fraction and infarct size. Future studies should consider quantitative analyses of both first-pass perfusion and late gadolinium enhancement imaging in the evaluation of novel therapies targeted to the microvasculature of the infarct-related artery.

Increase in creatinine and cardiovascular risk in patients with systolic dysfunction after myocardial infarction.

Baseline renal function is a potent independent risk factor for adverse events after acute myocardial infarction (MI). Worsening renal function (WRF) has been shown to influence outcomes in the heart failure population, but its impact on cardiovascular risk in the post-MI period has not been well defined. For assessment of the prognostic importance of WRF, 2231 patients who had left ventricular dysfunction and were enrolled in the Survival and Ventricular Enlargement (SAVE) trial were studied. Patients were randomly assigned between 3 and 16 d (average 11 d) after acute MI to receive captopril or placebo; those with a serum creatinine of >2.5 mg/dl were excluded from SAVE. WRF was defined as an increase in creatinine of >0.3 mg/dl measured from baseline to 2 wk after randomization. The predictive value of WRF on cardiovascular morbidity and mortality was examined during 42 mo of follow-up. Paired serum creatinine measurements at baseline and 2 wk were available in 1854 patients. WRF occurred in 223 (12.0%) patients and was a stronger predictor of death (hazard ratio [HR] 1.46; 95% confidence interval [CI] 1.05 to 2.02) than baseline creatinine (HR 1.31; 95% CI 1.01 to 1.70). WRF also showed an increased risk for cardiovascular death (HR 1.62; 95% CI 1.14 to 2.30) and the composite end point (HR 1.32; 95% CI 1.03 to 1.70). When stratified by treatment, 104 (5.7%) and 116 (6.4%) patients with WRF in the placebo and captopril groups had no significant association between treatment group and WRF (P = 0.38). The risk for death associated with WRF was HR 1.63 (95% CI 1.05 to 2.52) in the placebo group compared with HR 1.33 (95% CI 0.81 to 2.21) in the captopril group (P = 0.49 for interaction). WRF as early as 2 wk after MI was not uncommon (12.0%) and was associated with increased mortality in patients without renal dysfunction at baseline. Patients who received captopril did not demonstrate more WRF than patients who received placebo. Monitoring serum creatinine in patients during the first few weeks after MI may help to identify those who are at highest risk and guide effective long-term therapeutic choices.

Association of QRS duration and outcomes after myocardial infarction: the VALIANT trial.

BACKGROUND: Prolongation of the QRS duration has been shown to be associated with adverse outcomes among heart failure (HF) patients. The association of QRS duration with clinical outcomes in the post-myocardial infarction (MI) setting is less well defined. OBJECTIVES: To assess the prognostic significance of QRS duration prolongation on initial electrocardiogram after acute MI. METHODS: QRS duration was measured in 403 patients with MI complicated by left ventricular dysfunction, signs or symptoms of HF, or both, who were enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) echo study. The cohort was divided into quartiles of QRS duration (<75 ms, 75-88 ms, 89-108 ms, >108 ms). The number of clinical events were determined and compared across the groups. RESULTS: Increasing QRS duration is associated with a higher incidence of HF, sudden death (SD), and cardiovascular (CV) death (P-trend <0.05) but not with stroke or recurrent MI. The univariate relative risks for HF, SD, and CV death with increasing QRS duration quartiles were 1.31 (95% CI, 1.06-1.64), 1.57 (95% CI, 1.03-2.40), and 1.31 (95% CI, 1.03-1.66), respectively, but QRS duration did not remain independently predictive of adverse outcome after adjusting for the 10 most predictive baseline covariates. Baseline end-diastolic and end-systolic volumes were larger and ejection fraction was lower in the higher QRS quartile groups. CONCLUSIONS: Prolonged QRS duration, even within the normal range, is associated with larger ventricular volumes, reduced systolic function, and an increased risk for development of HF, SD, and CV death after MI but appears to be a marker, rather than an independent predictor, for increased risk.

Risk assessment in patients with depressed left ventricular function after myocardial infarction using the myocardial performance index--Survival and Ventricular Enlargement (SAVE) experience.

BACKGROUND: Myocardial performance index (MPI) is a noninvasive, quantitative Doppler measure of global cardiac function, integrating systolic and diastolic functions. The prognostic significance of MPI is less clear for cardiovascular (CV) events after myocardial infarction (MI) among individuals at high risk with depressed left ventricular (LV) systolic function. METHODS: We analyzed echocardiograms from 512 patients with depressed LV function after MI enrolled in the Survival and Ventricular Enlargement (SAVE) echocardiographic substudy. Baseline MPI measures were obtainable in 226 patients. The cohort was separated by median MPI (0.50). MPI was related to baseline clinical and echocardiographic characteristics, ventricular remodeling, and subsequent CV events, including recurrent MI, heart failure, CV death, and a composite of all CV end points. RESULTS: An MPI of 0.5 or more was associated with larger infarct size and reduced LV systolic function at baseline; other baseline characteristics between the groups were similar. A total of 64 (28.3%) patients experienced CV events. Baseline MPI did not influence ventricular remodeling and did not modify the relationship between ventricular dilatation and CV events. After covariate adjustment, an MPI of 0.50 or higher remained an independent predictor for adverse CV events (hazard ratio [HR], 2.00, 95% confidence interval 1.17-3.43). CONCLUSIONS: An MPI of 0.50 or greater is an independent predictor for CV events after MI in patients with known LV dysfunction.