Therapeutic Advances in Cardiovascular Disease

Adenosine is the first-line medication in patients with paroxysmal supraventricular tachycardia. Because it is cleared so rapidly from the circulation, recurrence of paroxysmal supraventricular tachycardia after initial successful conversion may occur.

This study was conducted to evaluate the role of oral verapamil administration to control early recurrences of paroxysmal supraventricular tachycardia after adenosine infusion.

Patients with acute paroxysmal supraventricular tachycardia and no contraindications for adenosine or verapamil treatment were included in study. All patients received an adenosine protocol (6 mg rapid bolus intravenous injection followed by two repeated doses of 12 mg if necessary). Patients in the adenosine-only group did not received any other medications but patients in the adenosine/verapamil group received 40 mg verapamil orally immediately after converting the rhythm to sinus rhythm. All patients were followed up for 6 h in the acute care area of the emergency department under continuous cardiac monitoring.

A total of 113 patients were assessed for eligibility and 92 patients were randomized into two groups (adenosine only versus adenosine/verapamil). There was no statistically significant difference in paroxysmal supraventricular tachycardia recurrence rate between the two groups in the first 30 min after treatment. Recurrence rate was statistically significantly lower in the adenosine/verapamil group than in the adenosine-only group between 30 and 120 min after treatment and thereafter. Two patients in the adenosine-only group experienced flushing and one patient in the adenosine/verapamil group experienced decreased systolic blood pressure.

Oral verapamil can decrease paroxysmal supraventricular tachycardia recurrence after successful control with intravenous adenosine.

The objective of this study was to determine the molecular mechanisms by which cardiac Rho-associated coiled-coil containing protein kinase (ROCK) activation after myocardial infarction (MI) does intervene in cardiac systolic function decline and remodeling.

Simultaneous measurement of different cardiac ROCK target proteins levels, in vivo left ventricular (LV) systolic function, myocardial fibrosis and hypertrophy in rats with MI under ROCK inhibition with fasudil.

Seven days after MI, the ventricular mass increased significantly by 5.6% in the MI group and was reduced with fasudil. LV systolic dysfunction improved significantly with fasudil whereas cardiac ROCK activation was reduced to sham levels. The ROCK inhibitor also reduced increased cardiac levels of both ROCK1 and ROCK2 isoforms, cardiomyocyte ROCK2 fluorescence levels and β-myosin heavy chain (MHC) levels in addition to myocardial collagen volume fraction decline. Compared with sham rats, troponin phosphorylation levels after MI were similar and ROCK inhibition reduced them. MI significantly increased phosphorylation levels of extracellular-signal-regulated kinase (ERK) 42 and ERK 44 by twofold and 63%, respectively, whereas in the fasudil-treated MI group these levels were similar to those in the sham group. MI significantly increased phosphorylated levels of the transcription factor GATA-4 and the ROCK inhibitor normalized them.

LV systolic dysfunction after MI was strongly associated with cardiac ROCK activation and subsequent phosphorylation of ROCK target proteins that promote ventricular remodeling such as β-MHC and the ERK/GATA-4 pathway. ROCK inhibition with fasudil significantly improved systolic function, diminished myocardial fibrosis and normalized β-MHC and ERK/GATA-4 phosphorylation levels.

Oxidative stress is currently considered to be the key factor in doxorubicin-induced cardiotoxicity. Comparatively small quantity of the endogenous antioxidant content of the heart is assumed to be the predisposing factor for doxorubicin-induced cardiotoxicity. The present research was designed to evaluate the antioxidant potential and tumor necrosis factor alpha-(TNF-α) inhibiting activity of sesame oil against acute doxorubicin-induced cardiotoxicity.

Male Wistar albino rats (180–200 g) were administered sesame oil in two dissimilar doses (5 and 10 ml/kg body weight, orally) for 30 days, followed by a single dose of doxorubicin (30 mg/kg s.c.).

In the doxorubicin-treated group, increased oxidative stress was proven by a significant rise of thiobarbituric acid reactive substances level and a decrease of myocardial superoxide dismutase, catalase and reduced glutathione content. Histopathological studies showed myocardial necrosis with accumulation of inflammatory cells, vacuolization and overall enlargement of the myocardium. Western blot analysis showed marked expression of TNF-α in the myocardium. Alteration in biochemical parameters by doxorubicin administration was prevented significantly (p < 0.0001) in the 5 and 10 ml/kg sesame oil treated rat hearts. Treatment with 5 and 10 ml/kg of sesame oil reduced the doxorubicin-induced TNF-α expression in the myocardium, which was associated with reduced myocyte injury. The overall effect of sesame oil was comparable with probucol, which shows similar protection.

The chronic oral administration of sesame oil prevents acute doxorubicin-induced cardiotoxicity by enhancing cardiac endogenous antioxidants and decreasing myocardial TNF-α expression.

The aim of this study was to evaluate the use of as-needed (PRN) labetalol and hydralazine [intravenous (IV) or oral] in hospitalized medicine patients for the treatment of severe asymptomatic hypertension and to examine the potential negative outcomes associated with their use.

The electronic health record of 250 medicine patients hospitalized at the University of Colorado Hospital between November 2014 and April 2016 who received at least one dose of PRN IV or oral hydralazine or labetalol were retrospectively reviewed. The primary outcome was to describe the use of PRN antihypertensive medications in this population.

A total of 573 PRN doses of antihypertensive medication were administered. Oral hydralazine was the most common (521 doses, 90.9%). A total of 36% of PRN administrations were given for a systolic blood pressure (SBP) <180 mmHg and diastolic blood pressure (DBP) <110 mmHg (cut-point for acute severe hypertension). No serious adverse events were related to PRN antihypertensive administration. Despite receiving at least one PRN antihypertensive medication during hospitalization, 40.8% of patients were not continued on their home antihypertensive medication(s) while hospitalized, and 62.4% of patients did not have their home regimens intensified at discharge.

As-needed oral hydralazine is frequently prescribed for acute blood pressure lowering with administration thresholds often less than what are used to define acute severe hypertension. Many patients are prescribed PRN antihypertensive medication instead of being continued on their home regimens, and most patients do not have the intensity of their home regimens increased. Providers need to be educated about the use of PRN antihypertensive medication for the management of severe asymptomatic hypertension in the hospital setting.

The guidelines for hypertension require the presence of compelling indications for pharmacological management of hypertension associated with various diseases. Data mainly obtained through randomized controlled trials have provided evidence supporting effectiveness of the combination of losartan (Lo) and hydrochlorothiazide (HCTZ) for management of hypertensive patients. However, there have been few reports discussing the effectiveness of Lo/HTCZ (losartan 50 mg/hydrochlorothizide 12.5 mg) in the ‘real world’ in the management of isolated systolic hypertension (ISH). This study was designed to investigate the ‘real world’ effectiveness of Lo/HTCZ-based treatment of ISH associated with various diseases.

This was a retrospective, uncontrolled analysis of data derived from a large, cross-sectional web-based clinical database collected by physicians.

Of 24,825 eligible patients, 20,726 were followed during a 6-month period. Among these, subjects for analysis included those with systolic blood pressure (SBP) >140 mmHg and diastolic BP (DBP) <90 mmHg; patients with diabetes mellitus and chronic kidney disease were excluded. A total of 15,846 patients were analysed. Among the various complications, hypercholesterolemia was the most frequent concomitant cardiovascular (CV) risk factor (48.1%), followed by obesity (16.3%). Associated clinical conditions were cerebrovascular diseases (9.6%), ischemic heart disease (7.9%) and left ventricular hypertrophy (4.6%). Total numbers of patients exhibiting any type of complications were 62% (≤64 years old), 69% (65–74 years old) and 67% (≥75 years old) (stratification of age). Mean SBP/DBP measurements (mm Hg) were 156/78 at the start, 140/72 at 1 month and 134/72 at 6 months. Blood pressure (BP) reductions associated with various diseases were similar among patients. Laboratory data including serum levels of total cholesterol, uric acid, hemoglobin A1c and serum potassium did not change during the study. Adverse effects such as orthostatic hypotension and considerable reductions in BP (>30 mmHg SBP) were rare.

Lo/HTCZ is safe and effective in reducing and improving BP control in a ‘real world’ setting. Treatment with Lo/HTCZ enabled a substantial proportion of hypertensive patients with associated diseases to achieve the recommended goal of <140 mm Hg.

To assess the efficacy and safety of once daily olmesartan medoxomil (OM)/amlodipine besylate (AM)/hydrochlorothiazide (HCTZ) 40/10/25 mg in patients with hypertension not at goal with mono, dual or triple drug therapy.

This was a single-center, prospective, open-label, blinded-endpoint study. After a 1-week screening visit, 40 patients were enrolled into the study and given once daily treatment with OM/AM/HCTZ after the patients underwent baseline ambulatory blood pressure monitoring (ABPM) on their original therapy. The primary endpoint was changes from baseline in mean 24 h ABPM [systolic blood pressure (SBP)] after the first day of therapy with OM/AM/HCTZ 40/10/25 mg. Secondary endpoints were changes from baseline in mean 24 h ABPM [diastolic blood pressure (DBP)] after the first day of therapy with OM/AM/HCTZ 40/10/25 mg; mean changes from baseline in trough seated SBP (SeSBP) at day 1 and SeSBP at weeks 1, 2, 3 and 4; mean changes from baseline in trough seated DBP (SeDBP) at day 1 and SeDBP at weeks 1, 2, 3 and 4; and the percentage of subjects achieving mean 24 h, daytime and night-time ABPM BP goals.

The baseline paired t-test systolic ABPM was 134.0 ± 2.77 mmHg and day 1 was 128.6 ± 2.47 mmHg with a treatment difference of −5.55 ± 1.3 mmHg (p<0.0001). At week 1, paired t-test ABPM SBP reduction was 117.7 ± 2.0 mmHg with a treatment difference of −16.5 ± 1.8 mmHg (p < 0.0001). At week 2, paired t-test ABPM SBP reduction was 115.8 ± 1.8 mmHg with a treatment difference of −18.4 ± 2.0 mmHg (p < 0.0001). At week 3, paired t-test ABPM SBP reduction was 115.5 ± 1.9 mmHg with a treatment difference of −18.6 ± 2.0 mmHg (p < 0.0001). At week 4, paired t-test ABPM SBP reduction was 115.5 ± 1.8 mmHg with a treatment difference of −18.6 ± 2.2 mmHg (p < 0.0001). The baseline paired t-test SeSBP was 142 ± 2.43 mmHg and day 1 was 132 ± 2.59 mmHg with a treatment difference of −9.78 ± 1.51 mmHg (p < 0.0001). At week 1, paired t-test SeSBP reduction was 124.0 ± 1.6 mmHg with a treatment difference of −17.9 ± 1.8 mmHg (p < 0.0001). At week 2, paired t-test SeSBP reduction was 120.3 ± 1.7 mmHg with a treatment difference of −21.5 ± 2.1 mmHg (p < 0.0001). At week 3, paired t-test SeSBP reduction was 118.5 ± 1.8 mmHg with a treatment difference of −23.3 ± 1.7 mmHg (p < 0.0001). At week 4, paired t-test SeSBP reduction was 119.6 ± 1.7 mmHg with a treatment difference of −22.2 ± 1.9 mmHg (p < 0.0001).

Treatment with OM/AM/HCTZ achieved superior (SBP) ABPM reductions compared with mono, dual or triple drug therapy, resulting in all patients achieving systolic ABPM goal without ABPM documented hypotension.