5 MID Study
5 Year Mortality in Patients with Left Ventricular Diastolic Dysfunction and Preserved Ejection Fraction
Catholic Health System, Buffalo, NY
Salim H Memon M.B.B.S.Yuji Saito M.D., Ph.D., F.A.C.C.
Background
Epidemiological Importance
Olmsted County, Minnesota
2042 randomly selected residents (mean age 63)
5.6% had moderate or severe diastolic dysfunction with normal EF
Cleveland Clinic study
36,261 adults (mean age 58) with LVEF ≥55%
65.2 % had diastolic dysfunction
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Background
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Clinical Importance
Asymptomatic
Risk factor for DHF / HFpEF
Heart failure
Prevalence of more than 5 million
50% have DHF / HFpEF
Background
Prognostic Importance
Limited Studies available
Increased Mortality with DD (3 significant studies)
No increased Mortality with Mild/Grade 1 DD
No mortality reducing drugs up to date
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Background
Types of LV Dysfunction
• Systolic - Impaired cardiac contractility
• Diastolic - Abnormal cardiac relaxation, stiffness or filling
Distinct disorders
Not a continuous spectrum of disorders
Can co-exist
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Background
Terminology• Diastolic Dysfunction• Diastolic Heart Failure• Heart Failure with Preserved Ejection Fraction
(HFpEF)
Characteristics:• Normal LVEF• Normal LV end-diastolic volume• Abnormal diastolic function
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Diagnosis and Grading
Requires Comprehensive assessment using Echocardiography
• Transmitral Doppler inflow velocity patterns• Pulmonary venous Doppler flow patterns• Tissue Doppler velocities• Color M-mode flow propagation velocity
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• Study Design• Study Flow Diagram• Outcome Measures• Methods• Statistical Analyses used• Results• Conclusions• Strengths and Limitations• Future Considerations• References• Acknowledgements
Study Design
• Case Control Retrospective Analysis
• Comparison of patients with normal and abnormal diastolic function in terms of all cause mortality over 60 months from the date of 2-Dimensional Echocardiogram
• Institutional Review Board Approval
• Sisters of Charity Hospital
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Study Design
Inclusion Criteria:• Age ≥ 18
• 2-D Echocardiogram between Dec’07 – Dec’08
• Preserved Ejection Fraction (≥50%)
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Study Design
Exclusion Criteria:• LV Ejection Fraction < 50%• Atrial Fibrillation• Unable to assess Diastolic function • Unavailable Mortality Data• Severe Mitral Valve Disease• History of Mitral Valve Surgery• Two 2D-Echocardiograms (2nd Echo excluded)
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3018 Patients who has 2-Dimensional Echocardiograms from Dec’07 to Dec’08 were assessed for eligibility for the study
Study Flow Diagram
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2107 Patients were excluded LV Ejection Fraction < 50%Atrial FibrillationUnable to assess Diastolic function Unavailable Mortality DataSevere Mitral Valve DiseaseHistory of Mitral Valve Surgery 911 Patients included
250 Had normal diastolic function
661 Had diastolic dysfunction (abnormal diastolic dysfunction)
Followed for 60 months for all cause mortality
Statistical Analyses• IBM Statistical Package for Social Sciences
(SPSS) software V.20• Continuous data expressed as Mean with 1 SD• Categorical – Number (%)• Analyze Group Differences:Continuous Variables: ANOVA
Categorical Variables: χ² tests
• Kaplin – Meier Curves – Unadjusted Survival• Cox Regression Survival Analyses for adjusted
survival5 MID Study
Baseline Demographic and Clinical Characteristics
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Characteristic No DD (N = 250)
Grade 1 DD(N = 340)
Grade 2 DD(N = 308)
Grade 3 DD(N = 13)
Total (N = 911) p-value
Age – yr 62.6 ± 15.4 73.7 ± 11.1 69.7 ± 13.1 75.7 ± 15.4 <0.001
Male – No. (%) 76 (30.4%) 111 (32.6%) 116 (37.7%) 2 (15.4%) 321 (33.5%) 0.139
CAD – No. (%) 48 (19.2%) 83 (26.1%) 78 (27.4%) 3 (25.0%) 212 (24.5%) 0.138
HTN – No. (%) 179 (71.6%) 249 (78.3%) 228 (80.0%) 11 (91.7%) 667 (77.1%) 0.062
Hypercholestrolemia – No. (%) 115 (46.0%) 190 (59.7%) 154 (54.0%) 6 (50.0%) 465 (53.8%) 0.013
Diabetes Mellitus-NIDDM – No. (%)-IDDM – No. (%)
43 (17.2%)27 (10.8%)
48 (15.1%)41 (12.9%)
52 (18.2%)38 (13.3%)
3 (25.0%)3 (25.0%)
146 (16.9%)109 (12.6%)
0.6410.462
Total no. of Coronary Risk Factors
1.65 ± 1.16 1.92 ± 1.08 1.93 ± 1.16 2.17 ± 1.11 0.012
Race-Caucasian-African American-Other
163 (65.2%)77 (30.8%)
10 (4%)
305 (89.7%)24 (7.1%)11 (3.2%)
258 (83.8%)35 (11.4%)15 (4.9%)
11 (84.6%)1 (7.7%)1 (7.7%)
737 (80.9%)137 (15.0%)
37 (4.0%)
<0.001
Baseline Demographic and Clinical Characteristics
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Characteristic No DD (N = 250)
Grade 1 DD(N = 340)
Grade 2 DD(N = 308)
Grade 3 DD(N = 13)
Total (N = 911) p-value
Age – yr 62.6 ± 15.4 73.7 ± 11.1 69.7 ± 13.1 75.7 ± 15.4 <0.001
Male – No. (%) 76 (30.4%) 111 (32.6%) 116 (37.7%) 2 (15.4%) 321 (33.5%) 0.139
CAD – No. (%) 48 (19.2%) 83 (26.1%) 78 (27.4%) 3 (25.0%) 212 (24.5%) 0.138
HTN – No. (%) 179 (71.6%) 249 (78.3%) 228 (80.0%) 11 (91.7%) 667 (77.1%) 0.062
Hypercholestrolemia – No. (%) 115 (46.0%) 190 (59.7%) 154 (54.0%) 6 (50.0%) 465 (53.8%) 0.013
Diabetes Mellitus-NIDDM – No. (%)-IDDM – No. (%)
43 (17.2%)27 (10.8%)
48 (15.1%)41 (12.9%)
52 (18.2%)38 (13.3%)
3 (25.0%)3 (25.0%)
146 (16.9%)109 (12.6%)
0.6410.462
Total no. of Coronary Risk Factors
1.65 ± 1.16 1.92 ± 1.08 1.93 ± 1.16 2.17 ± 1.11 0.012
Race-Caucasian-African American-Other
163 (65.2%)77 (30.8%)
10 (4%)
305 (89.7%)24 (7.1%)11 (3.2%)
258 (83.8%)35 (11.4%)15 (4.9%)
11 (84.6%)1 (7.7%)1 (7.7%)
737 (80.9%)137 (15.0%)
37 (4.0%)
<0.001
Echocardiograhic Characteristics Degree of Diastolic Dysfunction →
Grade 1 Grade 2 Grade 3 p ValueEchocardiograhic Characteristics ↓
E-wave velocity (cm/s) 68 ± 16 87 ± 26 114 ± 25 <0.001
A-wave velocity (cm/s) 101 ± 23 97 ± 29 45 ± 14 <0.001
E/A Velocity Ratio 0.68 ± 0.18 0.92 ± 0.19 2.6 ± 0.59 <0.001
Medial e' wave velocity (cm/s) 9.8 ± 3.8 9.6 ± 3.9 8.2 ± 2.5 0.405
E/e' (medial) Velocity Ratio 8.12 ± 4.54 10.78 ± 5.96 15.53 ± 5.34 <0.001
IVRT (ms) 99 ± 25 85 ± 22 61 ± 19 <0.001
Deceleration Time (ms) 293 ± 75 247 ± 63 178 ± 39 <0.001
Left Atrial Size (cm) 3.7 ± 0.8 4.1 ± 0.6 4.7 ± 0.7 <0.001
Inter Ventricular Septum Size (cm) 1.15 ± 0.36 1.12 ± 0.24 1.22 ± 0.35 0.026
Posterior Wall Size (cm) 1.11 ± 0.25 1.09 ± 0.22 1.22 ± 0.35 <0.001
LV Diameter - End Diastolic (cm) 4.4 ± 0.7 4.6 ± 0.7 5.0 ± 0.7 <0.001
LV Ejection Fraction (%) 61 ± 6 61± 6 62 ± 6 0.027
RVSP (mm Hg) 35 ± 10 40 ± 13 47 ± 13 <0.001
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Outcome: Normal Function vs DD
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Vital Status →
Alive Deceased TotalDiastolic Dysfunction ↓
Present – No. (%) 445 (67.3) 216 (32.7) 661 (100)
Absent – No. (%) 181 (72.4) 69 (27.6) 250 (100)
Total – No. (%) 626 (68.7) 285 (31.3) 911 (100)
Outcome: Normal Function vs DD
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Vital Status →
Alive Deceased TotalDiastolic Dysfunction ↓
Present – No. (%) 445 (67.3) 216 (32.7) 661 (100)
Absent – No. (%) 181 (72.4) 69 (27.6) 250 (100)
Total – No. (%) 626 (68.7) 285 (31.3) 911 (100)
Diastolic Dysfunction as Risk for all cause mortality: Hazard Ratio = 1.325 (1.005 – 1.748) p-value = 0.046
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Outcome:Normal Function vs different grades of DD
Vital Status →
Alive Deceased TotalGrade of DD ↓
None – No. (%) 181 (72.4) 69 (27.6) 250 (100)
Grade 1 – No. (%) 235 (69.1) 105 (30.9) 340 (100)
Grade 2 – No. (%) 204 (66.2) 104 (33.8) 308 (100)
Grade 3 – No. (%) 6 (46.2) 7 (53.8) 13 (100)
Total – No. (%) 626 (68.7) 285 (31.3) 911 (100)
Outcome:Normal Function vs different grades of DD
Vital Status →
Alive Deceased TotalGrade of DD ↓
None – No. (%) 181 (72.4) 69 (27.6) 250 (100)
Grade 1 – No. (%) 235 (69.1) 105 (30.9) 340 (100)
Grade 2 – No. (%) 204 (66.2) 104 (33.8) 308 (100)
Grade 3 – No. (%) 6 (46.2) 7 (53.8) 13 (100)
Total – No. (%) 626 (68.7) 285 (31.3) 911 (100)
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Outcome:Normal Function vs different grades of DD
Grade of Diastolic Dysfunction
Hazard Ratio (95% CI) p value
Grade 1 / Mild 1.177 (0.859 – 1.612) 0.309
Grade 2 / Moderate 1.363 (1.001 – 1.857) 0.049
Grade 3 / Severe 2.416 (1.075 – 5.434) 0.033
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Outcome:Normal Function vs different grades of DD
Grade of Diastolic Dysfunction
Hazard Ratio (95% CI) p value
Grade 1 / Mild 1.177 (0.859 – 1.612) 0.309
Grade 2 / Moderate 1.363 (1.001 – 1.857) 0.049
Grade 3 / Severe 2.416 (1.075 – 5.434) 0.033
Conclusions
• Moderate and severe Left Ventricular DD with preserved ejection fraction was associated with worsened 5-year all-cause mortality.
• Mortality was worse when DD was more severe.
• Mild DD had no significant impact on survival.
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Strengths and Limitations
Strengths:• Long follow up• One of the very few mortality studies based on grades of
Left Ventricular Diastolic Dysfunction• Good number of subjects in the cohort
Limitations:• Retrospective nature• Single Geographical Location• Unequal representation of both genders
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Future Considerations
Can Diastolic Dysfunction be defined a significant precursor for development of DHF?
As Impaired Fasting Glucose or Impaired Glucose Tolerance is for Diabetes Mellitus
As Prehypertension is for Hypertension
Can aggressive control of DD risk factors prevent progression to DHF?
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References• Burden of systolic and diastolic ventricular dysfunction in the community:
appreciating the scope of the heart failure epidemic; Redfield MM et al; JAMA. 2003;289(2):194.
• Mortality rate in patients with diastolic dysfunction and normal systolic function; Halley CM et al; Arch Intern Med. 2011;171(12):1082.
• Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251-9. [PMID: 16855265]
• Lam CS, Donal E, Kraigher-Krainer E, Vasan RS. Epidemiology and clinical course of heart failure with preserved ejection fraction. Eur J Heart Fail. 2011;13:18-28. [PMID: 20685685]
• Mitral ratio of peak early to late diastolic filling velocity as a predictor of mortality in middle-aged and elderly adults: the Strong Heart Study; Bella JN et al; Circulation. 2002;105(16):1928
• www.biodigital.com• http://www.learntheheart.com/GADD-echoClassification.html5 MID Study
AcknowledgementsContinuous support and mentoring• Dr. Khalid Qazi• Dr. Henri Woodman• Dr. Azhar Supariwala
Institutional Review Board• Dr. Sateesh Satchidanand• Danielle Casucci• Catholic Health System – IRB
Echo Lab Staff at Sisters of Charity Hospital
5 MID Study