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CLINICAL STUDY

Effect of Right Ventricular Function andPulmonary Pressures on Heart FailurePrognosisSrilakshmi M. Adhyapak, DNB

The relationship of right ventricular function and pulmonary systolic pressure in patients with con- gestive heart failure was evaluated to risk-stratifythem. The study included 147 consecutive patients with symptomatic heart failure whounderwent clinical and laboratory examination and echocardiography including Doppler tissueechocardiography. They were followed for amean of 11.2 6.4 months. During follow-up, 16 patients died and 45 patients had nonfatal cardiac events. There were 60 readmissions for heart failure. Pulmonary artery systolic pressure and right ventricular systolic function wereinversely related (r 2 =0.66, P< .001). On Coxmultivariate survival analysis, early worsening of pulmonary arterial pressures was an indepen- dent prognostic predictor (hazard ratio, 0.44; condence interval, 0.280.91, P=.024). The patients with pulmonary hypertension and right ventricular systolic dysfunction had the worst prognosis. The assessments of right ventricular function help to risk-stratify patients with heart failure. The early worsening of pulmonary hypertension is a powerful predictor of worse prognosis. Prev Cardiol. 2010;13:7277.

2009 Wiley Periodicals, Inc.

In patients with primary (idiopathic) dilated car-diomyopathy (DCM) or ischemic heart disease(IHD), left ventricular (LV) dysfunction is the ori-ginal physiologic disorder leading to the clinicalsyndrome of chronic heart failure. A reduced LVejection fraction is a powerful predictor of death

in a general population of patients with heart fail-ure; however, its prognostic value loses strengthwhen applied to patients with advanced heartfailure. 1

Recent studies 28 have demonstrated thatreduced right ventricular (RV) ejection fraction isan independent prognostic factor in moderate tosevere heart failure. Combined RV systolic and dia-stolic dysfunction are strong predictors of poorprognosis in symptomatic heart failure. 9 Pulmonaryhypertension frequently complicates heart failureand is considered an indicator of worse prognosisirrespective of RV function. 1012

We sought to examine the relationship of RVsystolic function and pulmonary artery systolic pres-sure in symptomatic patients with heart failure, by2-dimensional echocardiography and Doppler tissueechocardiography, in order to risk-stratify them.

METHODSPatientsThe study population comprised 147 consecutivepatients with symptomatic heart failure. The studyperiod was December 2004 to June 2007. Institu-tional ethics committee approval was obtained, andinformed consent was obtained from all studypatients. All patients were in sinus rhythm and inmoderate to severe heart failure as dened by the Fra-mingham criteria, with an etiology of DCM or IHD.

DCM was dened as LV dysfunction in theabsence of signicant coronary artery disease( 70% luminal narrowing) on coronary angiogra-phy or absence of pathological Q waves on electro-cardiography and absence of long-standing diabetesmellitus, valvular heart disease, myocardial disease,or active myocarditis. IHD was diagnosed on thebasis of documented previous myocardial infarctionor signicant coronary artery disease on coronaryangiography.

Exclusion CriteriaPatients with valvular heart disease, cardiac amyloido-sis, hypertrophic cardiomyopathy, active alcoholism,

From the Department of Cardiology, St. Johns MedicalCollege Hospital, Bangalore, India Address for correspondence:Srilakshmi M. Adhyapak, DNB(Cardiology), Departmentof Cardiology, St. Johns Medical College Hospital, Bangalore 560034, India E-mail: srili2881967@yahoo.com Manuscript received May 28, 2009; revised July 24, 2009; accepted August 7, 2009

doi: 10.1111/j.1751-7141.2009.00053.x

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chronic obstructive pulmonary disease, malignancy,advanced liver or renal disease, recent myocardialinfarction ( < 6 months), or unstable angina wereexcluded. Patients receiving parenteral inotropes atpresentation were also excluded. Patients with atrialbrillation and RV pacing were excluded.

All patients underwent routine blood chemistryand hematologic tests, 12-lead electrocardiography,chest radiography, and standard 2-dimensional andtissue Doppler echocardiography. The clinical vari-ables are presented in Table I.

Echocardiography All echocardiographic measurements were obtainedon the General Electric Vivid 3 (Milwaukee, WI)equipped with a phased array transducer of 2.5MHz frequency. Echocardiography was performedat entry into the study and once in 2 weeks duringthe study period. Standard 2-dimensional echocardi-

ography and pulsed Doppler tissue imaging of thetricuspid and mitral annular motion were obtainedin all patients.

The 2-dimensional measurements were per-formed as recommended by the American Societyof Echocardiography. 20 All values were indexed tobody surface area. LV ejection fraction (EF) wasdetermined by the modied biplane Simpsons rule.Impaired LV function was dened as LVEF 45%.

Doppler tissue measurements were performedwith the patients in the left lateral decubitus posi-tion, during shallow respiration. The sample volumewas placed on the tricuspid annulus, with care

taken to obtain an ultrasound beam parallel to thedirection of tricuspid annular motion. Similarrecordings were obtained at the mitral annulus.Peak systolic (Sa), peak early (Ea) and late (Aa) dia-stolic tricuspid, and mitral annular velocities, alongwith simultaneous electrocardiogram were recordedat a speed of 50 mm s. All measurements wereobtained on 3 to 6 consecutive heart cycles, and themean value was calculated.

Pulsed Doppler tracings of the tricuspid inowand RV outow were obtained simultaneously fromthe apical 5-chamber view with upward tilt of thetransducer, held at the apex. The RV ejection time(ET) was measured from onset to the end of theRV outow Doppler velocity prole below thebaseline. The isovolumetric relaxation time (IVRT)was measured from cessation of the RV outow tothe onset of the tricuspid inow velocity proleabove the baseline. The isovolumetric contractiontime (IVCT) was measured from the cessation of the tricuspid inow to the onset of RV outowvelocity prole above the baseline. The RV myocar-dial performance index (MPI) was calculated by theformula: IVCT + IVRT ET.

Based on the values of the pulmonary artery sys-tolic pressure (PASP) derived from the continuousTR velocity envelope and RV function based on theRV Sa, the study group was classied into 4 sub-

groups: group 1, normal PASP preserved RV func-tion; group 2, normal PASP RV dysfunction; group3, high PASP preserved RV function; and group 4,high PASP RV dysfunction.

The mitral inow pulsed Doppler values werealso noted. The pressure gradient between rightventricle and right atrium was calculated from theTR velocity envelope, and 5 to 10 mm Hg wasadded as right atrial pressure, depending on the dis-tensibility of the inferior vena cava in the subxi-phoid views. A mean pulmonary artery pressure> 25 mm Hg at rest was dened as pulmonaryhypertension. The patients with pulmonary hyper-tension and RV dysfunction at entry into studywere subjected to high-resolution CT scans to ruleout pulmonary thromboembolism. All echocardi-ography was performed by 2 experienced sonog-raphers who were blinded to the results of thestudy.

Table I. Clinical Characteristics of the Study Group(N=147)

Age, y 54 16.9Male female 135 12New York Heart Association functional class

2 653 604 22

Etiology DCM 75 (51%)IHD 72 (49%)LVIDd 46 7 mm m2

LVIDs 26 6 mm m2

LVEF 39% 8%PASP 56.3 8.9 mm Hg RV Sa 11.8 3.6 cm sRV MPI 0.8 0.7HTN 52%

DM 57%Therapy Diuretics 100% ACEIs 92%Digitalis 73%Nitrates 49%Spironolactone 38%b-Blockers 35% Antiplatelets 47%Oral anticoagulants 34%

Abbreviations: ACEI, angiotensin-converting enzymeinhibitor; DCM, dilated cardiomyopathy; DM, diabetesmellitus; HTN, hypertension; IHD, ischemic heart

disease; LVEF, left ventricular ejection fraction; LVIDd,left ventricular internal diameter in diastole; LVIDs, leftventricular internal diameter in systole; PASP, pulmonary artery systolic pressure; RV Sa, right ventricular annularsystolic wave by tissue Doppler imaging; RV MPI, rightventricular myocardial performance index.

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Follow-Up

The patients were followed up for cardiac mortalityand nonfatal cardiac events relating to heart failure.Serial echocardiography was performed at 2-weekintervals. Cardiac death was dened as death due toheart failure, myocardial infarction, malignant ar-rhythmias, or cardiac arrest. Heart failure requiringhospitalization was identied as exacerbation of dyspnea, need for parenteral diuretic therapy, andsymptoms associated with left or right heart failure.Survival was dened as freedom from cardiac-related death. Event-free survival was dened asfreedom from combined end point (cardiac-relateddeath and hospitalization for heart failure).

Statistical AnalysisContinuous variables were expressed as mean standard deviation. Categoric variables wereexpressed as frequencies. The best maximum likeli-hood estimates of the cutoffs for parameters of interest were obtained by a receiver operating char-acteristic curve analysis. The continuous variablesamong the 4 groups were compared using analysisof variance, and categoric variables were comparedusing chi-square test. Correlations between PASPand variables quantifying RV function were doneusing linear regression analysis. Survival analysiswas performed according to the Cox regressionmethod. Cumulative survival was obtained accord-

ing to the presence or absence of pulmonary hyper-

tension or RV dysfunction. A P value