Clinical trial NCT00939640: Effects of the Dietary Approaches to Stop Hypertension(DASH) Sodium-restricted Diet in Diastolic Heart Failure
Official title: Effects of the Dietary Approaches to Stop Hypertension(DASH) Sodium-restricted Diet on Ventriculovascular Function in Heart Failure With Preserved Systolic Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diastolic Heart Failure
Hypertensive Heart Disease
Keywords: Diet
Sodium
Hypertension
Potassium
Antioxidants
congestive heart failure
Heart failure with normal ejection fraction
Heart failure with preserved systolic function
Lead sponsor: University of Michigan
Sponsor class: OTHER
First posted: 2009-07-15
Enrollment: 14
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Heart failure with preserved systolic function (HF-PSF, or 'diastolic heart failure') accounts for half of hospitalizations for heart failure in patients over the age of 65. Most HF-PSF patients have systemic hypertension (HTN), and characteristic HTN-induced cardiovascular changes contribute to HF-PSF. However, it is unclear why most patients with HTN never develop HF-PSF or which specific aspects of HTN predispose to HF-PSF.

In the Dahl S rat, the primary animal model of HF-PSF, high dietary sodium intake suppresses the systemic renin-angiotensin-aldosterone system, but upregulates renal and cardiac renin-angiotensin-aldosterone system by inducing oxidative stress. In humans, the magnitude of blood pressure response to sodium ingestion and depletion can categorize subjects as "salt-resistant" and "salt-sensitive." Human salt sensitivity is associated with structural and loading conditions that increase the risk for HF-PSF, including HTN, ventricular hypertrophy and diastolic dysfunction, arterial stiffening, and increased plasma volume. High dietary sodium intake induces oxidative stress in salt-sensitive humans. In humans with HTN and normal ventricular systolic function that do not have heart failure, increased oxidative stress predicts impaired exercise capacity, ventricular hypertrophy, diastolic dysfunction, arterial stiffening, and vascular endothelial dysfunction. The investigators have proposed that "salt sensitivity" and the accompanying oxidative stress on the typical high-sodium Western diet may contribute to the initiation and progression of HF-PSF.

In patients with HF-PSF, the investigators will relate dietary changes to biochemical and cardiovascular functional measures. The investigators will study subjects on ad-lib diet and and following three weeks of rigorous dietary modification with the Dietary Approaches to Stop Hypertension (DASH)/sodium-restricted diet (SRD). This diet is richer in natural antioxidants and lower in sodium than the usual American diet. The DASH/SRD is recommended to lower blood pressure in patients with HTN, and is particularly effective in elderly, obese, and salt-sensitive hypertensives. Dietary sodium restriction is recommended for all HF patients including those with HF-PSF. The investigators hypothesize that the DASH/SRD will have favorable effects on oxidative stress, ventricular and vascular function, and blood pressure control in patients with hypertensive HF-PSF.


Eligibility criteria: Inclusion Criteria:

* Satisfy European Society of Cardiology guidelines for the diagnosis of HF-PSF (Paulus WJ et al. Eur. Heart J. 2007;28:2539-2550).
* Framingham criteria for heart failure satisfied
* left ventricular ejection fraction ≥ 50% (contrast ventriculography, echocardiography, nuclear scintigraphy)
* Diastolic dysfunction on previous echocardiogram/catheterization or evidence of abnormal neurohormonal activation (B-type natriuretic peptide (BNP) ≥ 100 pg/ml) with supporting evidence (atrial fibrillation, left atrial enlargement, left ventricular hypertrophy)
* History of systemic hypertension
* Willing to adhere to provided diet

Exclusion Criteria:

* New York Heart Association Class IV heart failure symptoms
* Hospitalization for decompensated heart failure within past one month
* Uncontrolled hypertension (seated systolic blood pressure ≥ 180 or diastolic blood pressure ≥ 110) at rest, on current antihypertensive regimen
* Changes in medical regimen for heart disease or hypertension within past 1 month, including diuretic dose adjustment
* Primary exercise limitation due to severe pulmonary disease
* Poor echocardiographic windows
* Worse than moderate mitral or aortic stenosis or insufficiency.
* Serum potassium level \> 5.0 mmol/L at baseline or prior history of serum potassium level \> 6.0
* Serum calcium/phosphorus product \> 50 at baseline
* Severe renal insufficiency (current estimated glomerular filtration rate \< 30 ml/min)
* Severe anemia (hemoglobin \< 9 g/dL)
* Uncontrolled diabetes mellitus (hemoglobin A1c \> 9%)
* Non-hypertensive cause of HF-PSF, e.g. amyloidosis, sarcoidosis, constrictive pericardial syndromes
* Myocardial infarction or unstable angina, including new or worsening anginal syndrome, within the past three months
* Uncontrolled arrhythmia (including non rate-controlled atrial fibrillation)
* Terminal illness expected to result in death within six months or active solid-organ cancer
* Psychiatric disorder or dementia with potential to compromise dietary adherence

Primary outcomes:
measure: Brachial Artery Flow-mediated Dilation (FMD)
timeFrame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
Secondary outcomes:
measure: Mean 24-hour Systolic Blood Pressure
timeFrame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
measure: Diurnal Variation in Ambulatory Blood Pressure
timeFrame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
measure: Aortic Augmentation Index
timeFrame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
measure: Carotid-femoral Pulse Wave Velocity
timeFrame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
measure: Ventricular Diastolic Function
timeFrame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
measure: Six Minute Walk Test Distance
timeFrame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
measure: Urinary 8-isoprostanes
timeFrame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
Other outcomes:
measure: EndoPAT Arterial Endothelial Function
timeFrame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
measure: Estimated Glomerular Filtration Rate, Serum Potassium, Serum Calcium-phosphorus Product
timeFrame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Scott L Hummel, MD MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 Jul 20;355(3):251-9. doi: 10.1056/NEJMoa052256.
citation: Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003 Jan 8;289(2):194-202. doi: 10.1001/jama.289.2.194.
citation: Klotz S, Hay I, Zhang G, Maurer M, Wang J, Burkhoff D. Development of heart failure in chronic hypertensive Dahl rats: focus on heart failure with preserved ejection fraction. Hypertension. 2006 May;47(5):901-11. doi: 10.1161/01.HYP.0000215579.81408.8e. Epub 2006 Apr 3.
citation: Laffer CL, Bolterman RJ, Romero JC, Elijovich F. Effect of salt on isoprostanes in salt-sensitive essential hypertension. Hypertension. 2006 Mar;47(3):434-40. doi: 10.1161/01.HYP.0000202480.06735.82. Epub 2006 Jan 23.
citation: Dekleva M, Celic V, Kostic N, Pencic B, Ivanovic AM, Caparevic Z. Left ventricular diastolic dysfunction is related to oxidative stress and exercise capacity in hypertensive patients with preserved systolic function. Cardiology. 2007;108(1):62-70. doi: 10.1159/000095883. Epub 2006 Sep 25.
citation: Yugar-Toledo JC, Bonalume Tacito LH, Ferreira-Melo SE, Sousa W, Consolin-Colombo F, Irigoyen MC, Franchini K, Coelho OR, Moreno H Jr. Low-renin (volume dependent) mild-hypertensive patients have impaired flow-mediated and glyceryl-trinitrate stimulated vascular reactivity. Circ J. 2005 Nov;69(11):1380-5. doi: 10.1253/circj.69.1380.
citation: Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER 3rd, Simons-Morton DG, Karanja N, Lin PH; DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001 Jan 4;344(1):3-10. doi: 10.1056/NEJM200101043440101.
citation: Paulus WJ, Tschope C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbely A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J. 2007 Oct;28(20):2539-50. doi: 10.1093/eurheartj/ehm037. Epub 2007 Apr 11.
citation: Hummel SL, Seymour EM, Brook RD, Sheth SS, Ghosh E, Zhu S, Weder AB, Kovacs SJ, Kolias TJ. Low-sodium DASH diet improves diastolic function and ventricular-arterial coupling in hypertensive heart failure with preserved ejection fraction. Circ Heart Fail. 2013 Nov;6(6):1165-71. doi: 10.1161/CIRCHEARTFAILURE.113.000481. Epub 2013 Aug 28.
citation: Hummel SL, Seymour EM, Brook RD, Kolias TJ, Sheth SS, Rosenblum HR, Wells JM, Weder AB. Low-sodium dietary approaches to stop hypertension diet reduces blood pressure, arterial stiffness, and oxidative stress in hypertensive heart failure with preserved ejection fraction. Hypertension. 2012 Nov;60(5):1200-6. doi: 10.1161/HYPERTENSIONAHA.112.202705. Epub 2012 Oct 1.
citation: Mathew AV, Seymour EM, Byun J, Pennathur S, Hummel SL. Altered Metabolic Profile With Sodium-Restricted Dietary Approaches to Stop Hypertension Diet in Hypertensive Heart Failure With Preserved Ejection Fraction. J Card Fail. 2015 Dec;21(12):963-7. doi: 10.1016/j.cardfail.2015.10.003. Epub 2015 Oct 20.