Isosorbide Hydralazine Research Articles

Effectiveness of a Reminder in Improving Adherence With Outpatient Heart Failure Guideline Prescribing

Lack of guideline adherence in medication prescribing is a concern for heart failure patients with reduced ejection fraction. The purpose of this study is to evaluate the effectiveness of a provider reminder tool with decision support in prescribing for outpatients. A pre-post interventional design was used to measure prescribing and titration of class I medications with implementation of the tool in a convenience sample (N = 120) of consecutive provider-patient encounters. Compliance with renin-angiotensin-aldosterone system inhibitors, beta blockers, and hydralazine–isosorbide dinitrate improved. Compliance to mineralocorticoid receptor antagonists showed significant improvement. Uptitration of beta blockers and renin-angiotensin-aldosterone system inhibitors was achieved.

Hydralazine–Isosorbide Dinitrate Use in Patients With End-Stage Kidney Disease on Dialysis

IntroductionThe combination of hydralazine–isosorbide dinitrate (H-ISDN) has potential as a heart failure (HF) therapy in the setting of maintenance dialysis.MethodsIn this retrospective study, we analyzed the efficacy of H-ISDN using United States Renal Data System (USRDS) data. We identified all adult patients with a history of HF on maintenance dialysis between January 1, 2011, and December 31, 2016, with at least 1 prescription for H-ISDN. Baseline characteristics, prescriptions, and outcomes were retrieved from institutional and physician claims. The primary outcome was death from any cause. Additional outcomes included cardiovascular death, sudden cardiac death, hospitalization for HF, an inpatient diagnosis of myocardial infarction (MI), or new-onset atrial fibrillation. Stabilized inverse probability weights were estimated using relevant baseline characteristics and were used in Cox proportional hazards regression.ResultsWe identified 6306 patients who were treated with H-ISDN and 75,509 patients who did not receive H-ISDN. The crude all-cause mortality rate was lower in patients treated with H-ISDN (16.0 events/100 patient years [PYs]) than in nonusers (27.9/100-PY). H-ISDN use was independently associated with lower mortality: hazard ratio (HR) 0.48 (95% CI 0.43–0.54). Cardiovascular death and sudden cardiac death were less common among H-ISDN users than nonusers, Weighted HR was 0.62 (95% CI 0.53–0.71) and 0.62 (95% CI 0.52–0.73), respectively. In contrast, HF admission and MI were more frequent in patients treated with H-ISDN (195.5 and 18.0 events/100-PY) compared with nonusers (73.4 and 10.2 events/100-PY).ConclusionH-ISDN therapy may improve cardiovascular outcomes in maintenance dialysis patients with HF.

All-Cause Mortality as an End Point for Heart Failure With Preserved Ejection Fraction: Underperformance or Overambitious?

All-Cause Mortality as an End Point for Heart Failure With Preserved Ejection Fraction: Underperformance or Overambitious?

A Systematic Review and Network Meta-Analysis of Pharmacological Treatment of Heart Failure With Reduced Ejection Fraction

ObjectivesThis study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction. BackgroundThe estimated treatment effects of various combinations of contemporary HF medical therapies are not well characterized. MethodsWe performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between January 1987 and January 2020. We included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers (BB), mineralocorticoid receptor antagonists (MRAs), digoxin, hydralazine-isosorbide dinitrate, ivabradine, angiotensin receptor–neprilysin inhibitors (ARNi), sodium glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv-mecarbil. The primary outcome was all-cause death. We estimated the life-years gained in 2 HF populations (BIOSTAT-CHF [BIOlogy Study to TAilored Treatment in Chronic Heart Failure] and ASIAN-HF [Asian Sudden Cardiac Death in Heart Failure Registry]). ResultsWe identified 75 relevant trials representing 95,444 participants. A combination of ARNi, BB, MRA, and SGLT2i was most effective in reducing all-cause death (HR: 0.39; 95% CI: 0.31-0.49); followed by ARNi, BB, MRA, and vericiguat (HR: 0.41; 95% CI: 0.32-0.53); and ARNi, BB, and MRA (HR: 0.44; 95% CI: 0.36-0.54). Results were similar for the composite outcome of cardiovascular death or first hospitalization for HF (HR: 0.36; 95% CI: 0.29-0.46 for ARNi, BB, MRA, and SGLT2i; HR: 0.44; 95% CI: 0.35-0.56 for ARNi, BB, MRA, and omecamtiv-mecarbil; and HR: 0.43; 95% CI: 0.34-0.55 for ARNi, BB, MRA, and vericiguat). The estimated additional number of life-years gained for a 70-year-old patient on ARNi, BB, MRA, and SGLT2i was 5.0 years (2.5-7.5 years) compared with no treatment in secondary analyses. ConclusionsIn patients with HF with reduced ejection fraction, the estimated aggregate benefit is greatest for a combination of ARNi, BB, MRA, and SGLT2i.

Hydralazine-Isosorbide Dinitrate Associated with Reduced All-Cause and Cardiovascular Mortality in Patients on Dialysis with Heart Failure

Hydralazine-Isosorbide Dinitrate Associated with Reduced All-Cause and Cardiovascular Mortality in Patients on Dialysis with Heart Failure

Captopril Versus Hydralazine-Isosorbide Dinitrate Vasodilator Protocols in Patients With Acute Decompensated Heart Failure Transitioning From Sodium Nitroprusside

The role of oral vasodilators in the management of acute decompensated heart failure (ADHF) is not clearly defined. We evaluated the use of captopril vs hydralazine-isosorbide dinitrate (H-ISDN) in the transition from sodium nitroprusside (SNP) in patients with ADHF. A retrospective chart review was performed of 369 consecutive adult patients in the intensive care unit with ADHF and reduced ejection fraction, who received either a captopril or an H-ISDN protocol to transition from SNP. Captopril patients were matched 1:2 to H-ISDN patients, based on serum creatinine and race (Black vs non-Black). Baseline demographics, serum chemistry and use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) were similar in both groups. Time to SNP discontinuation (46.9 vs 40.4 hours, P = 0.11) and length of hospital stay (9.86 vs 7.99 days, P = 0.064) were similar in both groups. Length of hospital stay in the intensive care unit was statistically shorter in the H-ISDN group (4.11 vs 3.96 days, P = 0.038). Fewer H-ISDN protocol patients were discharged on ACEis/ARBs (82.9 % vs 69.9%, P = 0.003) despite similar kidney function at time of discharge (serum creatinine 1.1 vs 1.2, P = 0.113). No difference was observed in rates of readmission (40.7% vs 50%, P = 0.09) or mortality (16.3% vs 17.5 %, P = 0.77) at 1 year postdischarge. Similar inpatient and 1-year outcomes were observed between patients using H-ISDN vs ACEi when transitioning from SNP, even though fewer H-ISDN protocol patients were discharged taking ACEis/ARBs despite similar kidney function.

Use of Isosorbide Dinitrate/Hydralazine in the Pediatric Cardiac Population

<h3>Purpose</h3> The combination of isosorbide dinitrate/hydralazine (ISDN/HYD) offers direct arterial and venous vasodilation without adversely affecting renal function. It is used as an adjunct to standard heart failure therapies in adults with reduced ejection fraction. ISDN/HYD is an attractive option in pediatric cardiac patients who may not tolerate angiotensin converting enzyme inhibitors due to renal dysfunction from inadequate systemic cardiac output, nephrotoxic medications, or young age. Given the lack of published reports of its use in children, we report our experience with ISDN/HYD in a heterogeneous population of pediatric cardiac patients. <h3>Methods</h3> From an internal database, we identified all patients treated with ISDN/HYD. Patient characteristics at ISDN/HYD initiation, 3-months, discontinuation, and latest follow-up were abstracted from the chart. ISDN/HYD was dosed TID at a dose ratio of 1:2 ISDN:HYD. <h3>Results</h3> There were 59 patients treated with ISDN/HYD for a mean duration of 14 ± 14 months. Patient characteristics are summarized in Table 1. The mean age was 3.8 years, while those with single ventricle anatomy were mostly infants. Over half had a prior diagnosis of acute kidney injury. The majority of patients were initiated during a hospitalization. In addition to heart failure, ISDN/HYD was used in stage 1 single ventricle patients to reduce pulmonary over-circulation. Brain natriuretic peptide decreased from initiation to 3 months (782 vs 312 pg/mL, p=0.0007, n = 42), and left ventricular fractional shortening increased (29 vs 32%, p=0.013, n=32). <h3>Conclusion</h3> As demonstrated in this case series, ISDN/HYD is used across a heterogeneous pediatric cardiac population where acute kidney injury is common. Short-term follow up after ISDN/HYD initiation showed a reduction in BNP and a modest improvement in left ventricular systolic function. Further study is needed to define indications, side effects, and better understand outcomes of ISDN/HYD use in the pediatric cardiac population.

Why we love heart failure: an introduction to the universal definition of heart failure

“Stat rosa pristina nomine, nomina nuda tenemus” “The rose of old remains only through its name and we hold only bare names.” Umberto Eco. Il nome della rosa We both started to think about, and to research on, HF about 40 years ago, right with the publication of the first edition of Braunwald's textbook in 1980. That textbook was so clear. It was the first time for us that we found all essentials of pathophysiology, diagnosis and therapy of heart disease so clearly shown in one place.3 It was also the first time that we found a definition of HF usable in everyday clinical work and this was the time that we both fell in love with this syndrome. A name, a definition, may not be all, but it comes close. We define a syndrome. We have something to defeat. As more as we contemplate medicine, as more it seems that it is done by names and clear definitions. One of the most recent and devastating diseases we had, coronavirus disease 2019, was soon very clearly defined by a name, COVID-19, and while we still did not know anything of this disease, we could start searching in PubMed or Google for COVID-19 plus whatever is of interest and everything started coming out in increased clarity. HF was also not clear before we started having a definition. It was already clearly important but we did not have a clear enemy behind the name of HF. Dr Braunwald clearly defined HF and it was the first time we had something clear to fight against. Then, the methodology of randomized controlled trials was applied to HF and we had further definitions. The Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) enrolled patients with a diagnosis of HF ‘… based on clinical criteria: a history of heart disease with symptoms of dyspnea or fatigue or both, together with signs of fluid retention and no evidence of primary pulmonary disease. The patients were symptomatic at rest (NYHA functional class IV). (…) Measurements of myocardial function were not required.’4 Better patients' characterization started in the Veterans Administration Cooperative Study comparing hydralazine–isosorbide dinitrate combination with prazosin and placebo.5 Eligibility for this trial ‘was based on evidence of cardiac dilatation at (…) chest x-ray film or (..) echocardiography or left ventricular (…) radionuclide ejection fraction <45% in association with reduced exercise tolerance, as assessed by a progressive maximal bicycle-ergometer exercise test’.5 Then, measurement of left ventricular ejection fraction (LVEF) became widely available through echocardiography and the Studies of Left Ventricular Dysfunction (SOLVD) introduced the criterion of a low LVEF, ‘of 0.35 or less’ as an integral component of the definition of HF.6 However, it was only in 1995 that the task force of the European Society of Cardiology (ESC) published guidelines for the diagnosis of HF which, as nicely stated by Braunwald, ‘went beyond symptoms’ and ‘also required objective evidence of cardiac dysfunction in the definition’.7 The figure in the Braunwald and Antman editorial outlines this: major discoveries and step forward in HF treatment went along with milestones in the definition of HF.2 Thus, nothing closer to truth than the quotation by Albert Einstein that Gregg Fonarow used in another enlightening recent editorial comment: ‘Many of the things you can count, don't count. Many of the things you can't count, really count.’8 There is no number in a definition, nothing that can be measured, but a definition can change our life and, hopefully, that of our patients, too.

Nitrates in combination with hydralazine in cardiorenal syndrome: a randomized controlled proof-of-concept study.

AimsCardiorenal syndrome (CRS) is a common problem of great morbidity and mortality. Hydralazine–isosorbide dinitrate (H‐ISDN) may be used in renal failure and may improve exercise capacity in heart failure (HF). Our proof‐of‐concept study aimed to evaluate early evidence of efficacy, safety, and feasibility of H‐ISDN compared with standard of care in CRS.Methods and resultsThis multi‐centre, single‐blind, randomized trial in Singapore enrolled CRS patients, defined as chronic HF with concomitant renal failure [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2]. The primary outcome was 6 min walk test (6MWT) distance measured at 6 months. Secondary outcomes included study feasibility; efficacy outcomes which included renal, cardiac, and endothelial functions, health‐related quality of life using Short Form‐36, clinical outcomes; and adverse events. Forty‐four patients [71 ± 10 years; 75% male; median (inter‐quartile range) N‐terminal prohormone brain natriuretic peptide 1346 (481–2272) pg/mL] with CRS (left ventricular ejection fraction 42 ± 12% and eGFR 46 ± 15 ml/min/1.73 m2) were randomized into two equal groups. Of these, 39 (89%) had hypertension, 27 (61%) had diabetes mellitus, and 17 (39%) had atrial fibrillation. Six (27%) discontinued H‐ISDN owing to intolerance and poor compliance. There was a trend towards improved 6MWT distance with H‐ISDN compared with standard of care at 6 months (mean difference 27 m; 95% CI, −12 to 66), with little differences in secondary efficacy outcomes. Giddiness and hypotension occurred more frequently with H‐ISDN, but HF hospitalizations and mortality were less.ConclusionsOur pilot study does not support the addition of H‐ISDN on top of standard medical therapy to improve exercise capacity in patients with CRS.

The DANish randomized, double-blind, placebo controlled trial in patients with chronic HEART failure (DANHEART): A 2 × 2 factorial trial of hydralazine-isosorbide dinitrate in patients with chronic heart failure (H-HeFT) and metformin in patients with chronic heart failure and diabetes or prediabetes (Met-HeFT)

ObjectivesThe DANHEART trial is a multicenter, randomized (1:1), parallel-group, double-blind, placebo-controlled study in chronic heart failure patients with reduced ejection fraction (HFrEF). This investigator driven study will include 1500 HFrEF patients and test in a 2 × 2 factorial design: 1) if hydralazine-isosorbide dinitrate reduces the incidence of death and hospitalization with worsening heart failure vs. placebo (H-HeFT) and 2) if metformin reduces the incidence of death, worsening heart failure, acute myocardial infarction, and stroke vs. placebo in patients with diabetes or prediabetes (Met-HeFT).MethodsSymptomatic, optimally treated HFrEF patients with LVEF ≤40% are randomized to active vs. placebo treatment. Patients can be randomized in either both H-HeFT and Met-HeFT or to only one of these study arms. In this event-driven study, it is anticipated that 1300 patients should be included in H-HeFT and 1100 in Met-HeFT and followed for an average of 4 years.ResultsAs of May 2020, 296 patients have been randomized at 20 centers in Denmark.ConclusionThe H-HeFT and Met-HeFT studies will yield new knowledge about the potential benefit and safety of 2 commonly prescribed drugs with limited randomized data in patients with HFrEF.

Underuse of hydralazine and isosorbide dinitrate for heart failure in patients of African ancestry: a cross-European survey.

AimsPopulation data indicate that one in 25 persons of African ancestry has heart failure, a condition with relatively high mortality of around 50% in 5 years. Combined hydralazine and isosorbide dinitrate added to conventional therapy in African ancestry patients with heart failure and reduced ejection fraction improves quality of life and reduces the rate of first hospitalization for heart failure by 33% and annual mortality by 43%. The objectives of this study were to quantify the use of this guideline‐recommended therapy in Europe and the potential effect of implementation gaps on mortality.Methods and resultsPrescription drug registration and utilization databases and population statistics were analysed in a cross‐European survey without language restriction. Main outcomes were the number of unique patients prescribed the fixed combination hydralazine–isosorbide dinitrate (primary) or both drugs (secondary) in Europe in 2015, and the excess mortality related to prescribing practices was estimated. The survey indicates that around 12 million persons of African ancestry live in Europe. It is estimated that 480 000 persons of this population group have heart failure, with 120 000 eligible for hydralazine and isosorbide dinitrate therapy. However, single‐pill hydralazine–isosorbide dinitrate is not authorized and therefore not dispensed in Europe in 2015. Out of the 25 European nations surveyed, the UK and the Netherlands are the only countries with major African ancestry populations where both hydralazine and isosorbide dinitrate are available for oral use, aside Norway, Sweden, and Finland. Hydralazine and isosorbide dinitrate are prescribed to <500 European patients in 2015. Thus, despite the recommendations of the European Society of Cardiology, the large majority of African‐European patients with heart failure do not receive this drug combination, potentially resulting in 4800 to 5800 excess deaths yearly.ConclusionsThe life‐saving, guideline‐recommended, adjunctive therapy for heart failure in African ancestry patients with hydralazine and isosorbide dinitrate is rarely used in Europe. This major evidence‐practice gap should urgently be overcome to reduce excess mortality in African‐European patients with heart failure.

FEWER DEATHS OR HOSPITALIZATIONS FOR HEART FAILURE USING HYDRALAZINE-ISOSORBIDE MONONITRATE COMPARED TO HYDRALAZINE-ISOSORBIDE DINITRATE IN PATIENTS WITH SYSTOLIC HEART FAILURE

Hydralazine-isosorbide dinitrate (H-ISDN) carries an indication for treating systolic heart failure (HF). Hydralazine-isosorbide mononitrate (H-ISMN) does not carry this indication, but is used nonetheless as ISMN is once a day, while ISDN is three times a day. How effective H-ISMN is compared to H-

Clinical Effectiveness of Hydralazine–Isosorbide Dinitrate in African-American Patients With Heart Failure

ObjectivesThis study sought to evaluate the effectiveness of hydralazine–isosorbide dinitrate (H-ISDN) in African Americans with heart failure (HF) with reduced ejection fraction (HFrEF). BackgroundAmong African-American patients with HFrEF, H-ISDN was found to improve quality of life and lower HF-related hospitalization and mortality rates in the A-HEFT (African-American Heart Failure Trial). Few studies have evaluated the effectiveness of this therapy in clinical practice. MethodsVeterans Affairs patients with a hospital admission for HF between 2007 and 2013 were screened. Inclusion criteria included African-American race, left ventricular ejection fraction <40%, and receipt of Veterans Affairs medications. Exclusions were documented contraindications to H-ISDN, creatinine >2.0 mg/dl, or intolerance to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Adjusted hazard ratios were calculated for patients who received H-ISDN 6-months before admission compared with patients who did not receive H-ISDN, by using inverse probability weighting of propensity scores and a time to death analysis for 18 months of follow-up. Propensity scores were generated using patients’ characteristics, left ventricular ejection fraction, laboratory values, and hospital characteristics. ResultsThe final cohort included 5,168 African-American patients with HF (mean age 65.2 years), with 15.2% treated with H-ISDN before index admission. After 18 months, there were 1,275 reported deaths (24.7%). The adjusted mortality rate at 18 months was 22.1% for patients receiving H-ISDN treatment and 25.2% for untreated patients (p = 0.009); adjusted hazard ratio: 0.85 (95% confidence interval: 0.73 to 1.00; p = 0.057). ConclusionsH-ISDN remains underused in African-American patients with HFrEF. In this cohort, the study found that H-ISDN use was associated with lower mortality rates in African-American patients with HFrEF when controlling for patient selection by using an inverse probability weighting of propensity scores.

269 - Clinical Effectiveness of Hydralazine-Isosorbide Dinitrate in Vha Heart Failure Patients by Ethnicity

269 - Clinical Effectiveness of Hydralazine-Isosorbide Dinitrate in Vha Heart Failure Patients by Ethnicity

New Management Strategies in Heart Failure.

Despite >100 clinical trials, only 2 new drugs had been approved by the US Food and Drug Administration for the treatment of chronic heart failure in more than a decade: the aldosterone antagonist eplerenone in 2003 and a fixed dose combination of hydralazine-isosorbide dinitrate in 2005. In contrast, 2015 has witnessed the Food and Drug Administration approval of 2 new drugs, both for the treatment of chronic heart failure with reduced ejection fraction: ivabradine and another combination drug, sacubitril/valsartan or LCZ696. Seemingly overnight, a range of therapeutic possibilities, evoking new physiological mechanisms, promise great hope for a disease that often carries a prognosis worse than many forms of cancer. Importantly, the newly available therapies represent a culmination of basic and translational research that actually spans many decades. This review will summarize newer drugs currently being used in the treatment of heart failure, as well as newer strategies increasingly explored for their utility during the stages of the heart failure syndrome.

Clinical Effectiveness of Hydralazine-Isosorbide Dinitrate Therapy in Patients With Heart Failure and Reduced Ejection Fraction: Findings From the Get With The Guidelines-Heart Failure Registry.

In clinical trials, hydralazine-isosorbide dinitrate (H-ISDN) for heart failure with reduced ejection fraction reduced morbidity and mortality among black patients and patients with intolerance to angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. The effectiveness of H-ISDN in clinical practice is unknown. Using data from a clinical registry linked with Medicare claims, we examined the use and outcomes of H-ISDN between 2005 and 2011 among older patients hospitalized with heart failure and reduced ejection fraction. We adjusted for demographic and clinical characteristics using Cox proportional hazards models and inverse probability weighting. Among 4663 eligible patients, 22.7% of black patients and 18.2% of patients not on an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker were newly prescribed H-ISDN therapy at discharge. By 3 years, the cumulative incidence rates of mortality and readmission were similar between treated and untreated patients. After multivariable adjustment, 3-year outcomes remained similar for mortality [black patients: hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.75-1.13; other patients: HR, 0.93; 95% CI, 0.79-1.09], all-cause readmission (black patients: HR, 0.98; 95% CI, 0.84-1.13; other patients: HR, 1.02; 95% CI, 0.90-1.17), and cardiovascular readmission (black patients: HR, 0.99; 95% CI, 0.82-1.19; other patients: HR, 0.94; 95% CI, 0.81-1.09). A post hoc analysis of Medicare Part D data revealed low postdischarge adherence to therapy. Guideline-recommended initiation of H-ISDN therapy at hospital discharge was uncommon, and adherence was low. For both black patients and patients of other races, there were no differences in outcomes between those treated and untreated at discharge.

Response and tolerance to oral vasodilator up-titration after intravenous vasodilator therapy in advanced decompensated heart failure.

The aim of this study was to assess the haemodynamic response and tolerance to aggressive oral hydralazine/isosorbide dinitrate (HYD/ISDN) up-titration after intravenous vasodilator therapy in advanced decompensated heart failure (ADHF). Medical records of 147 consecutive ADHF patients who underwent placement of a pulmonary artery catheter and received intravenous vasodilator therapy were reviewed. Intravenous sodium nitroprusside and sodium nitroglycerin as first-line agent for those with preserved blood pressures were utilized in 143 and 32 patients, respectively. Sixty-one percent of patients were converted to oral HYD/ISDN combination therapy through a standardized conversion protocol. These patients had a significantly higher admission mean pulmonary arterial wedge pressure compared with patients not converted (28 ± 7 vs. 25 ± 8 mmHg, respectively; P-value 0.024). Beneficial haemodynamic response to decongestive therapy, defined as low cardiac filling pressures and cardiac index ≥2.20 L/min/m(2) without emergent hypotension, was achieved in 32% and 29% of patients who did or did not receive oral HYD/ISDN, respectively (P-value 0.762). HYD/ISDN dosing was progressively and consistently decreased up to the moment of hospital discharge and during outpatient follow-up, primarily due to incident hypotension. The use of a standardized haemodynamically guided up-titration protocol for conversion from intravenous to oral vasodilators may warrant subsequent dose reductions upon stabilization.

Hydralazine and Organic Nitrates Restore Impaired Excitation-Contraction Coupling by Reducing Calcium Leak Associated with Nitroso-Redox Imbalance*

Although the combined use of hydralazine and isosorbide dinitrate confers important clinical benefits in patients with heart failure, the underlying mechanism of action is still controversial. We used two models of nitroso-redox imbalance, neuronal NO synthase-deficient (NOS1(-/-)) mice and spontaneously hypertensive heart failure rats, to test the hypothesis that hydralazine (HYD) alone or in combination with nitroglycerin (NTG) or isosorbide dinitrate restores Ca(2+) cycling and contractile performance and controls superoxide production in isolated cardiomyocytes. The response to increased pacing frequency was depressed in NOS1(-/-) compared with wild type myocytes. Both sarcomere length shortening and intracellular Ca(2+) transient (Δ[Ca(2+)]i) responses in NOS1(-/-) cardiomyocytes were augmented by HYD in a dose-dependent manner. NTG alone did not affect myocyte shortening but reduced Δ[Ca(2+)]i across the range of pacing frequencies and increased myofilament Ca(2+) sensitivity thereby enhancing contractile efficiency. Similar results were seen in failing myocytes from the heart failure rat model. HYD alone or in combination with NTG reduced sarcoplasmic reticulum (SR) leak, improved SR Ca(2+) reuptake, and restored SR Ca(2+) content. HYD and NTG at low concentrations (1 μm), scavenged superoxide in isolated cardiomyocytes, whereas in cardiac homogenates, NTG inhibited xanthine oxidoreductase activity and scavenged NADPH oxidase-dependent superoxide more efficiently than HYD. Together, these results revealed that by reducing SR Ca(2+) leak, HYD improves Ca(2+) cycling and contractility impaired by nitroso-redox imbalance, and NTG enhanced contractile efficiency, restoring cardiac excitation-contraction coupling.

USE OF HYDRALAZINE/ISOSORBIDE DINITRATE COMBINATION IN AFRICAN-AMERICAN AND OTHER RACE/ETHNIC GROUP PATIENTS WITH HEART FAILURE AND REDUCED LEFT VENTRICULAR EJECTION FRACTION

Hydralazine-isosorbide dinitrate (H-ISDN) therapy is recommended for African American patients with moderate to severe heart failure with reduced ejection fraction (<40%) (HFrEF), but use, temporal trends, and clinical characteristics associated with H-ISDN in clinical practice are unknown. An

What Is the Trigger for Hydralazine Isosorbide Use in Systolic Heart Failure?

What Is the Trigger for Hydralazine Isosorbide Use in Systolic Heart Failure?