Heart Failure With Preserved Ejection Fraction
Conditions
Brief summary
This study is designed as a multicenter, prospective, controlled, randomized, two-arms, cross-over, two parallel cohorts, efficacy Clinical research with CE-marked medical device . The crossover trial will be performed in a blind fashion, so each participant will be evaluated during both blinded pacing-on and pacing-off phases, each of which will last 3 months. The population includes patients with the diagnosis of stable HFpEF according to criteria of the European Society of Cardiology and New York Heart Association (NYHA) functional class II-III/IV, left ventricular hypertrophy with small ventricular volume, sinus rhythm with low basal heart rate and chronotropic incompetence (CI). All patients will undergo pacemaker implantation, and computer-generated randomization sequence previously designed will be used to allocate participants (in a 1:1 ratio) to receive: (a) programming of the pacemaker with pacing On followed by pacing Off in two periods of 3 months; or (b) programming of the pacemaker with pacing Off followed by pacing On in two periods of 3 months. The study will be conducted in three centers in Spain. Discounting the time due to staggered entry, the total duration of a patient's follow-up will be 7 months.
Interventions
DEVICEDual-chamber cardiac pacemaker (Essentio MRI L111 Boston Scientific®), Single-chamber cardiac pacemaker (Essentio MRI L110 Boston Scientific®)
Dual-chamber cardiac pacemaker (Essentio MRI L111 Boston Scientific®), with rate-adaptive pacing of the right atrium. There will be an associated right atrial lead (INGEVITY™ MRI Pacing Lead Boston®) and right ventricular lead (INGEVITY™ MRI Pacing Lead Boston®). Single-chamber cardiac pacemaker (Essentio MRI L110 Boston Scientific®), with rate-adaptive pacing of the ventricles. There will be a right ventricular lead (INGEVITY™ MRI P Boston®).
Sponsors
Fundación para la Investigación del Hospital Clínico de Valencia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stable symptomatic heart failure (NYHA functional class ≥II) during the last month. * Diagnosis criteria of HFpEF according to ESC guidelines: 1. symptoms and signs of HF. 2. left ventricular ejection fraction ≥50% by Simpson method. 3. proBNP \>125 pg/mL in the last month. 4. at least one additional criterion: 1. relevant structural heart disease (left ventricular hypertrophy and/or left atrial enlargement); and/or 2. Diastolic dysfunction. * Left ventricular hypertrophy was defined as wall thickness \> 10 mm. * Small ventricular volume was defined as indexed left ventricular end diastolic volume \< 45 ml/m2. * Adults ≥18 years old. * Previous admission for acute heart failure. * Chronotropic incompetence assessed by CPET, defined as: \[(HRmax - HRrest)\]/\[(220 - age) - (HRrest)\] \< 0.62. * Resting heart rate \< 65 bpm in sinus rhythm or 70 bmp in atrial fibrillation.
Exclusion criteria
* Inability to perform a valid baseline exercise test. * Significant primary pulmonary disease; including pulmonary arterial hypertension, chronic thromboembolic pulmonary disease or chronic obstructive pulmonary disease. * Patient with prior history of left ventricular ejection fraction \<50%. * History of an acute coronary syndrome in the previous 12 months. * Effort angina or signs of ischemia during CPET. * RER threshold at \<1.05 at the CPET. * Significant primary moderate to severe valvular disease. * Any other comorbidity with a life expectancy lower than 1 year. * Heart rate at rest \> 75 lpm. * Other pacemaker indication. * Pregnant women. * Baseline rhythm different from sinus rhythm or atrial fibrillation. * Active treatment with beta-blockers, digitalis or non dihidropiridine calcium channel blockers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak oxygen uptake | 3 months after the pacemarker stimulation | The primary endpoint of the study is absolute and relative changes in peak oxygen uptake (peakVO2) after three months of pacemaker stimulation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left ventricular volume index | From baseline until the end of study in month 7 | Absolute changes in echocardiogram parameters (Left ventricular volume index) |
| Left atrial volume index | From baseline until the end of study in month 7 | Absolute changes in echocardiogram parameters (Left atrial volume index) |
| Pro-B-type natriuretic peptide | From baseline until the end of study in month 7 | Absolute and relative changes in prognostic biomarkers (pro-B-type natriuretic peptide) |
| Serum carbohydrate antigen 125 | From baseline until the end of study in month 7 | Absolute and relative changes in prognostic biomarkers (serum carbohydrate antigen 125). |
| Minnesota Living with Heart Failure Questionnaire (MLHFQ) | From randomization until the end of study in month 7 | Absolute changes in quality of live assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ) |
| E/E' ratio | From baseline until the end of study in month 7 | Absolute changes in echocardiogram parameters (E/E' ratio) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Acute HF hospitalizations | From baseline until the end of study in month 7 | Total number of episodes of acute HF hospitalizations. |
| Worsening HF not requiring hospitalization | From baseline until the end of study in month 7 | Total episodes of worsening HF not requiring hospitalization |
| Mortality | From baseline until the end of study in month 7 | Mortality |
Countries
Spain
Contacts
Primary ContactJulio Núñez, Doctor
Backup ContactVicente Bertomeu, Doctor
Outcome results
None listed