Effect of Selective Heart Rate Slowing in Heart Failure With Preserved Ejection Fraction
BACKGROUND—Heart failure with preserved ejection fraction (HFpEF) is associated with significant morbidity and mortality but is currently refractory to therapy. Despite limited evidence, heart rate reduction has been advocated, on the basis of physiological considerations, as a therapeutic strategy...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2015-11, Vol.132 (18), p.1719-1725 |
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| creator | Pal, Nikhil Sivaswamy, Nadiya Mahmod, Masliza Yavari, Arash Rudd, Amelia Singh, Satnam Dawson, Dana K Francis, Jane M Dwight, Jeremy S Watkins, Hugh Neubauer, Stefan Frenneaux, Michael Ashrafian, Houman |
| description | BACKGROUND—Heart failure with preserved ejection fraction (HFpEF) is associated with significant morbidity and mortality but is currently refractory to therapy. Despite limited evidence, heart rate reduction has been advocated, on the basis of physiological considerations, as a therapeutic strategy in HFpEF. We tested the hypothesis that heart rate reduction improves exercise capacity in HFpEF.
METHODS AND RESULTS—We conducted a randomized, crossover study comparing selective heart rate reduction with the If blocker ivabradine at 7.5 mg twice daily versus placebo for 2 weeks each in 22 symptomatic patients with HFpEF who had objective evidence of exercise limitation (peak oxygen consumption at maximal exercise [(Equation is included in full-text article.)O2 peak] |
| doi_str_mv | 10.1161/CIRCULATIONAHA.115.017119 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4640051</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1730021810</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5479-fbbcadd55e1e6b4c984ee3705207bf1e3697c53632b6874ae6aff2dced14de0b3</originalsourceid><addsrcrecordid>eNqNUU1vEzEQtRCIhsJfQObGZVt7_ZU9gBRFCYkUUdQPwc3y7o4bF2dd7N1E_Pu6TVq1t55m5s17b0Z6CH2h5IRSSU-ny_Pp1WpyuTz7OVlMMiZOCFWUVm_QiIqSF1yw6i0aEUKqQrGyPEIfUrrJo2RKvEdHpWRsXAk5Qn9m1kLT42DxBfjcuS3gBZjY43PTA77wYee6a-y6Azo3zg8R8G_Xr_GvCAniFlo8u7nXhg7Po3loPqJ31vgEnw71GF3NZ5fTRbE6-7GcTlZFI7iqClvXjWlbIYCCrHlTjTkAU0SURNWWApOVagSTrKzlWHED0lhbtg20lLdAanaMvu99b4d6A3nR9dF4fRvdxsT_OhinX246t9bXYau55IQImg2-Hgxi-DdA6vXGpQa8Nx2EIWmqGCElHVOSqdWe2sSQUgT7dIYSfZ-MfplMxoTeJ5O1n5__-aR8jCITvu0Ju-B7iOmvH3YQ9RqM79evOHAHVeugxw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1730021810</pqid></control><display><type>article</type><title>Effect of Selective Heart Rate Slowing in Heart Failure With Preserved Ejection Fraction</title><source>MEDLINE</source><source>American Heart Association Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Journals@Ovid Ovid Autoload</source><creator>Pal, Nikhil ; Sivaswamy, Nadiya ; Mahmod, Masliza ; Yavari, Arash ; Rudd, Amelia ; Singh, Satnam ; Dawson, Dana K ; Francis, Jane M ; Dwight, Jeremy S ; Watkins, Hugh ; Neubauer, Stefan ; Frenneaux, Michael ; Ashrafian, Houman</creator><creatorcontrib>Pal, Nikhil ; Sivaswamy, Nadiya ; Mahmod, Masliza ; Yavari, Arash ; Rudd, Amelia ; Singh, Satnam ; Dawson, Dana K ; Francis, Jane M ; Dwight, Jeremy S ; Watkins, Hugh ; Neubauer, Stefan ; Frenneaux, Michael ; Ashrafian, Houman</creatorcontrib><description>BACKGROUND—Heart failure with preserved ejection fraction (HFpEF) is associated with significant morbidity and mortality but is currently refractory to therapy. Despite limited evidence, heart rate reduction has been advocated, on the basis of physiological considerations, as a therapeutic strategy in HFpEF. We tested the hypothesis that heart rate reduction improves exercise capacity in HFpEF.
METHODS AND RESULTS—We conducted a randomized, crossover study comparing selective heart rate reduction with the If blocker ivabradine at 7.5 mg twice daily versus placebo for 2 weeks each in 22 symptomatic patients with HFpEF who had objective evidence of exercise limitation (peak oxygen consumption at maximal exercise [(Equation is included in full-text article.)O2 peak] <80% predicted for age and sex). The result was compared with 22 similarly treated matched asymptomatic hypertensive volunteers. The primary end point was the change in (Equation is included in full-text article.)O2 peak. Secondary outcomes included tissue Doppler–derived E/e′ at echocardiography, plasma brain natriuretic peptide, and quality-of-life scores. Ivabradine significantly reduced peak heart rate compared with placebo in the HFpEF (107 versus 129 bpm; P<0.0001) and hypertensive (127 versus 145 bpm; P=0.003) cohorts. Ivabradine compared with placebo significantly worsened the change in (Equation is included in full-text article.)O2 peak in the HFpEF cohort (-2.1 versus 0.9 mL·kg·min; P=0.003) and significantly reduced submaximal exercise capacity, as determined by the oxygen uptake efficiency slope. No significant effects on the secondary end points were discernable.
CONCLUSION—Our observations bring into question the value of heart rate reduction with ivabradine for improving symptoms in a HFpEF population characterized by exercise limitation.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT02354573.</description><identifier>ISSN: 0009-7322</identifier><identifier>ISSN: 1524-4539</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/CIRCULATIONAHA.115.017119</identifier><identifier>PMID: 26338956</identifier><language>eng</language><publisher>United States: by the American College of Cardiology Foundation and the American Heart Association, Inc</publisher><subject>Aged ; Aged, 80 and over ; Asymptomatic Diseases ; Benzazepines - therapeutic use ; Biomarkers ; Cross-Over Studies ; Cyclic Nucleotide-Gated Cation Channels - antagonists & inhibitors ; Double-Blind Method ; Endpoint Determination ; Exercise Test ; Exercise Tolerance ; Female ; Heart Failure - blood ; Heart Failure - drug therapy ; Heart Failure - physiopathology ; Heart Rate - drug effects ; Humans ; Hypertension - blood ; Hypertension - drug therapy ; Hypertension - physiopathology ; Ivabradine ; Male ; Middle Aged ; Natriuretic Peptide, Brain - blood ; Original ; Oxygen Consumption - drug effects ; Sinoatrial Node - drug effects ; Sinoatrial Node - physiopathology ; Stroke Volume ; Treatment Failure</subject><ispartof>Circulation (New York, N.Y.), 2015-11, Vol.132 (18), p.1719-1725</ispartof><rights>2015 by the American College of Cardiology Foundation and the American Heart Association, Inc.</rights><rights>2015 The Authors.</rights><rights>2015 The Authors. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5479-fbbcadd55e1e6b4c984ee3705207bf1e3697c53632b6874ae6aff2dced14de0b3</citedby><cites>FETCH-LOGICAL-c5479-fbbcadd55e1e6b4c984ee3705207bf1e3697c53632b6874ae6aff2dced14de0b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3673,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26338956$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pal, Nikhil</creatorcontrib><creatorcontrib>Sivaswamy, Nadiya</creatorcontrib><creatorcontrib>Mahmod, Masliza</creatorcontrib><creatorcontrib>Yavari, Arash</creatorcontrib><creatorcontrib>Rudd, Amelia</creatorcontrib><creatorcontrib>Singh, Satnam</creatorcontrib><creatorcontrib>Dawson, Dana K</creatorcontrib><creatorcontrib>Francis, Jane M</creatorcontrib><creatorcontrib>Dwight, Jeremy S</creatorcontrib><creatorcontrib>Watkins, Hugh</creatorcontrib><creatorcontrib>Neubauer, Stefan</creatorcontrib><creatorcontrib>Frenneaux, Michael</creatorcontrib><creatorcontrib>Ashrafian, Houman</creatorcontrib><title>Effect of Selective Heart Rate Slowing in Heart Failure With Preserved Ejection Fraction</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>BACKGROUND—Heart failure with preserved ejection fraction (HFpEF) is associated with significant morbidity and mortality but is currently refractory to therapy. Despite limited evidence, heart rate reduction has been advocated, on the basis of physiological considerations, as a therapeutic strategy in HFpEF. We tested the hypothesis that heart rate reduction improves exercise capacity in HFpEF.
METHODS AND RESULTS—We conducted a randomized, crossover study comparing selective heart rate reduction with the If blocker ivabradine at 7.5 mg twice daily versus placebo for 2 weeks each in 22 symptomatic patients with HFpEF who had objective evidence of exercise limitation (peak oxygen consumption at maximal exercise [(Equation is included in full-text article.)O2 peak] <80% predicted for age and sex). The result was compared with 22 similarly treated matched asymptomatic hypertensive volunteers. The primary end point was the change in (Equation is included in full-text article.)O2 peak. Secondary outcomes included tissue Doppler–derived E/e′ at echocardiography, plasma brain natriuretic peptide, and quality-of-life scores. Ivabradine significantly reduced peak heart rate compared with placebo in the HFpEF (107 versus 129 bpm; P<0.0001) and hypertensive (127 versus 145 bpm; P=0.003) cohorts. Ivabradine compared with placebo significantly worsened the change in (Equation is included in full-text article.)O2 peak in the HFpEF cohort (-2.1 versus 0.9 mL·kg·min; P=0.003) and significantly reduced submaximal exercise capacity, as determined by the oxygen uptake efficiency slope. No significant effects on the secondary end points were discernable.
CONCLUSION—Our observations bring into question the value of heart rate reduction with ivabradine for improving symptoms in a HFpEF population characterized by exercise limitation.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT02354573.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Asymptomatic Diseases</subject><subject>Benzazepines - therapeutic use</subject><subject>Biomarkers</subject><subject>Cross-Over Studies</subject><subject>Cyclic Nucleotide-Gated Cation Channels - antagonists & inhibitors</subject><subject>Double-Blind Method</subject><subject>Endpoint Determination</subject><subject>Exercise Test</subject><subject>Exercise Tolerance</subject><subject>Female</subject><subject>Heart Failure - blood</subject><subject>Heart Failure - drug therapy</subject><subject>Heart Failure - physiopathology</subject><subject>Heart Rate - drug effects</subject><subject>Humans</subject><subject>Hypertension - blood</subject><subject>Hypertension - drug therapy</subject><subject>Hypertension - physiopathology</subject><subject>Ivabradine</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Natriuretic Peptide, Brain - blood</subject><subject>Original</subject><subject>Oxygen Consumption - drug effects</subject><subject>Sinoatrial Node - drug effects</subject><subject>Sinoatrial Node - physiopathology</subject><subject>Stroke Volume</subject><subject>Treatment Failure</subject><issn>0009-7322</issn><issn>1524-4539</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUU1vEzEQtRCIhsJfQObGZVt7_ZU9gBRFCYkUUdQPwc3y7o4bF2dd7N1E_Pu6TVq1t55m5s17b0Z6CH2h5IRSSU-ny_Pp1WpyuTz7OVlMMiZOCFWUVm_QiIqSF1yw6i0aEUKqQrGyPEIfUrrJo2RKvEdHpWRsXAk5Qn9m1kLT42DxBfjcuS3gBZjY43PTA77wYee6a-y6Azo3zg8R8G_Xr_GvCAniFlo8u7nXhg7Po3loPqJ31vgEnw71GF3NZ5fTRbE6-7GcTlZFI7iqClvXjWlbIYCCrHlTjTkAU0SURNWWApOVagSTrKzlWHED0lhbtg20lLdAanaMvu99b4d6A3nR9dF4fRvdxsT_OhinX246t9bXYau55IQImg2-Hgxi-DdA6vXGpQa8Nx2EIWmqGCElHVOSqdWe2sSQUgT7dIYSfZ-MfplMxoTeJ5O1n5__-aR8jCITvu0Ju-B7iOmvH3YQ9RqM79evOHAHVeugxw</recordid><startdate>20151103</startdate><enddate>20151103</enddate><creator>Pal, Nikhil</creator><creator>Sivaswamy, Nadiya</creator><creator>Mahmod, Masliza</creator><creator>Yavari, Arash</creator><creator>Rudd, Amelia</creator><creator>Singh, Satnam</creator><creator>Dawson, Dana K</creator><creator>Francis, Jane M</creator><creator>Dwight, Jeremy S</creator><creator>Watkins, Hugh</creator><creator>Neubauer, Stefan</creator><creator>Frenneaux, Michael</creator><creator>Ashrafian, Houman</creator><general>by the American College of Cardiology Foundation and the American Heart Association, Inc</general><general>Lippincott Williams & Wilkins</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20151103</creationdate><title>Effect of Selective Heart Rate Slowing in Heart Failure With Preserved Ejection Fraction</title><author>Pal, Nikhil ; Sivaswamy, Nadiya ; Mahmod, Masliza ; Yavari, Arash ; Rudd, Amelia ; Singh, Satnam ; Dawson, Dana K ; Francis, Jane M ; Dwight, Jeremy S ; Watkins, Hugh ; Neubauer, Stefan ; Frenneaux, Michael ; Ashrafian, Houman</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5479-fbbcadd55e1e6b4c984ee3705207bf1e3697c53632b6874ae6aff2dced14de0b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Asymptomatic Diseases</topic><topic>Benzazepines - therapeutic use</topic><topic>Biomarkers</topic><topic>Cross-Over Studies</topic><topic>Cyclic Nucleotide-Gated Cation Channels - antagonists & inhibitors</topic><topic>Double-Blind Method</topic><topic>Endpoint Determination</topic><topic>Exercise Test</topic><topic>Exercise Tolerance</topic><topic>Female</topic><topic>Heart Failure - blood</topic><topic>Heart Failure - drug therapy</topic><topic>Heart Failure - physiopathology</topic><topic>Heart Rate - drug effects</topic><topic>Humans</topic><topic>Hypertension - blood</topic><topic>Hypertension - drug therapy</topic><topic>Hypertension - physiopathology</topic><topic>Ivabradine</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Natriuretic Peptide, Brain - blood</topic><topic>Original</topic><topic>Oxygen Consumption - drug effects</topic><topic>Sinoatrial Node - drug effects</topic><topic>Sinoatrial Node - physiopathology</topic><topic>Stroke Volume</topic><topic>Treatment Failure</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pal, Nikhil</creatorcontrib><creatorcontrib>Sivaswamy, Nadiya</creatorcontrib><creatorcontrib>Mahmod, Masliza</creatorcontrib><creatorcontrib>Yavari, Arash</creatorcontrib><creatorcontrib>Rudd, Amelia</creatorcontrib><creatorcontrib>Singh, Satnam</creatorcontrib><creatorcontrib>Dawson, Dana K</creatorcontrib><creatorcontrib>Francis, Jane M</creatorcontrib><creatorcontrib>Dwight, Jeremy S</creatorcontrib><creatorcontrib>Watkins, Hugh</creatorcontrib><creatorcontrib>Neubauer, Stefan</creatorcontrib><creatorcontrib>Frenneaux, Michael</creatorcontrib><creatorcontrib>Ashrafian, Houman</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pal, Nikhil</au><au>Sivaswamy, Nadiya</au><au>Mahmod, Masliza</au><au>Yavari, Arash</au><au>Rudd, Amelia</au><au>Singh, Satnam</au><au>Dawson, Dana K</au><au>Francis, Jane M</au><au>Dwight, Jeremy S</au><au>Watkins, Hugh</au><au>Neubauer, Stefan</au><au>Frenneaux, Michael</au><au>Ashrafian, Houman</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Selective Heart Rate Slowing in Heart Failure With Preserved Ejection Fraction</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2015-11-03</date><risdate>2015</risdate><volume>132</volume><issue>18</issue><spage>1719</spage><epage>1725</epage><pages>1719-1725</pages><issn>0009-7322</issn><issn>1524-4539</issn><eissn>1524-4539</eissn><abstract>BACKGROUND—Heart failure with preserved ejection fraction (HFpEF) is associated with significant morbidity and mortality but is currently refractory to therapy. Despite limited evidence, heart rate reduction has been advocated, on the basis of physiological considerations, as a therapeutic strategy in HFpEF. We tested the hypothesis that heart rate reduction improves exercise capacity in HFpEF.
METHODS AND RESULTS—We conducted a randomized, crossover study comparing selective heart rate reduction with the If blocker ivabradine at 7.5 mg twice daily versus placebo for 2 weeks each in 22 symptomatic patients with HFpEF who had objective evidence of exercise limitation (peak oxygen consumption at maximal exercise [(Equation is included in full-text article.)O2 peak] <80% predicted for age and sex). The result was compared with 22 similarly treated matched asymptomatic hypertensive volunteers. The primary end point was the change in (Equation is included in full-text article.)O2 peak. Secondary outcomes included tissue Doppler–derived E/e′ at echocardiography, plasma brain natriuretic peptide, and quality-of-life scores. Ivabradine significantly reduced peak heart rate compared with placebo in the HFpEF (107 versus 129 bpm; P<0.0001) and hypertensive (127 versus 145 bpm; P=0.003) cohorts. Ivabradine compared with placebo significantly worsened the change in (Equation is included in full-text article.)O2 peak in the HFpEF cohort (-2.1 versus 0.9 mL·kg·min; P=0.003) and significantly reduced submaximal exercise capacity, as determined by the oxygen uptake efficiency slope. No significant effects on the secondary end points were discernable.
CONCLUSION—Our observations bring into question the value of heart rate reduction with ivabradine for improving symptoms in a HFpEF population characterized by exercise limitation.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT02354573.</abstract><cop>United States</cop><pub>by the American College of Cardiology Foundation and the American Heart Association, Inc</pub><pmid>26338956</pmid><doi>10.1161/CIRCULATIONAHA.115.017119</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 2015-11, Vol.132 (18), p.1719-1725 |
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| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload |
| subjects | Aged Aged, 80 and over Asymptomatic Diseases Benzazepines - therapeutic use Biomarkers Cross-Over Studies Cyclic Nucleotide-Gated Cation Channels - antagonists & inhibitors Double-Blind Method Endpoint Determination Exercise Test Exercise Tolerance Female Heart Failure - blood Heart Failure - drug therapy Heart Failure - physiopathology Heart Rate - drug effects Humans Hypertension - blood Hypertension - drug therapy Hypertension - physiopathology Ivabradine Male Middle Aged Natriuretic Peptide, Brain - blood Original Oxygen Consumption - drug effects Sinoatrial Node - drug effects Sinoatrial Node - physiopathology Stroke Volume Treatment Failure |
| title | Effect of Selective Heart Rate Slowing in Heart Failure With Preserved Ejection Fraction |
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