Figure 1 - available via license: Creative Commons Attribution 4.0 International
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(A) Episode of sustained ventricular tachycardia (cycle length 380 ms) which terminates after application of atnitachycardia pacing. (B) Episode of sustained ventricular tachycardia (cycle length 350 ms), resistant to atnitachycardia pacing. (C) Episode of ventricular fibrillation which terminates after application of high-energy DC shock.
Source publication
Key Clinical Message
Among implantable cardioverter‐defibrillator (ICD) recipients, there are patients with recurrent episodes of electrical storm (ES), retractable to the optimal antiarrhythmic drug therapy or invasive ablation procedures. A relatively novel anti‐ischemic drug with also antiarrhythmic properties, ranolazine, may effectively suppre...
Context in source publication
Context 1
... after the implantation, ES occurred with multiple episodes of sustained VT, requiring either antitachycardia pacing (ATP) or shock therapy for sinus rhythm restora- tion (Fig. 1). Intravenous amiodarone was administered acutely, followed by chronic per os intake. New episodes of ES occurred during the following period, with no detectable triggering condition. Two transvenous ablation procedures were performed within 6 months, both with- out success. In both electrophysiological studies, ventricu- lar ...
Citations
... The resultant reduction in intracellular Na + concentration partially inhibits the Na + /Ca 2+ exchange current, thus preventing the deleterious effect of intracellular Ca 2+ overload under the trigger of ischemia. 15 This indirect decrease in intracellular Ca 2+ concentration is responsible for the well-documented antianginal effect of ranolazine 14,16 and for the attenuation of toxicity due to sarcoendoplasmic reticulum calcium ATPase downregulation. 17 As previously described, ranolazine is able to protect the cardiac function from both doxorubicin-and trastuzumabrelated cardiotoxicity by reducing the effects of oxidative stress. ...
Purpose:
Pertuzumab, a novel anti-epidermal growth factor receptor 2 humanized monoclonal antibody, and trastuzumab-emtansine (TDM1), a novel antibody-drug conjugate made up of trastuzumab covalently linked to the highly potent microtubule inhibitory agent DM1, have been recently approved by the US Food and Drug Administration for increasing the efficiency and safety of breast cancer therapy with trastuzumab. We investigated for the first time the potential cardiotoxic effects of pertuzumab and TDM1, which are not yet fully elucidated, and we tested whether ranolazine could blunt their cardiotoxicity.
Methods:
The cardiotoxic effects were tested in vitro on rat cardiomyoblasts, human fetal cardiomyocytes, adult-like cardiomyocytes, and in vivo on a mouse model.
Results:
All the treated cardiac cell lines were significantly affected by treatment with the tested drugs. Surprisingly, TDM1 showed stronger inhibitory effects on cardiac cells with respect to trastuzumab and pertuzumab by more significantly reducing the cell viability and by changing the morphology of these cells. TDM1 also affected the beating phenotype of adult-like cardiomyocytes in vitro and reduced fractional shortening and ejection fraction in vivo in a mouse model. We also found that ranolazine attenuated not only the cardiotoxic side effects of trastuzumab but also those of pertuzumab and TDM1, when used in combinatorial treatments both in vitro and in vivo, as demonstrated by the recovery of fractional shortening and ejection fraction values in mice pretreated with TDM1.
Conclusion:
We demonstrated that it is possible to predict the eventual cardiotoxic effects of novel approved anticancer drugs early by using in vitro and in vivo approaches, which can also be useful to screen in advance the cardioprotective agents, so as to avoid the onset of unwanted cardiotoxic side effects.
... A total of 14 studies, [8][9][10][11][12][13][14][15][16][17][18][19][20][21] which reported data about the impact of ranolazine in ventricular arrhythmias, included in our systematic review ( Figure 1). Of these, 2 were randomized controlled trials (MERLIN-TIMI 36 and RAID), 1 was a randomized crossover trial (RYPPLE), 2 were observational studies, 1 was a case series, and 8 were case reports ( Table 1). ...
Ranolazine is a new medication for the treatment of refractory angina. However, except its anti-anginal properties, it has been found to act as an anti-arrhythmic. The aim of our systematic review is to present the existing data about the impact of ranolazine in ventricular arrhythmias. We searched MEDLINE and Cochrane databases as well clinicaltrials.gov until September 1, 2017 to find all studies (clinical trials, observational studies, case reports/series) reported data about the impact of ranolazine in ventricular arrhythmias. Our search revealed 14 studies (3 clinical trials, 2 observational studies, 8 case reports, 1 case series). These data reported a beneficial impact of ranolazine in ventricular tachycardia/fibrillation, premature ventricular beats, and ICD interventions in different clinical settings. The existing data highlight the anti-arrhythmic properties of ranolazine in ventricular arrhythmias.
Doxorubicin (Dox), a powerful chemotherapeutic agent, has been shown to cause cardiotoxicity and neurotoxicity. Ranolazine, a drug that is commonly used to treat patients with chronic angina, has been shown to reduce toxicity from Dox therapy. Therefore, the present study aims to investigate the mechanisms behind the protective effects of ranolazine on the heart and brain in Dox-treatment. Twenty-four male Wistar rats received 6 doses of either 0.9% normal saline (0.9% NSS, i.p., n = 8) or Dox (3 mg/kg, i.p., n = 16). All Dox-treated rats were assigned into 2 groups to receive vehicle (0.9% NSS, orally; n = 8) or ranolazine (305 mg/kg/day, orally; n = 8) for 30 consecutive days. Following the treatments, left ventricular (LV) function and cognition were determined. Animals were euthanized, then the heart and brain were collected for further analysis. Dox induced systemic oxidative stress/inflammation, and cardiac injury evidenced by mitochondrial dysfunction, mitochondrial dynamic imbalance, and apoptosis, resulting in LV dysfunction. Ranolazine significantly improved LV function via attenuating cardiac injury. Dox also caused brain pathologies as indicated by increased brain inflammation, impaired blood-brain barrier integrity, brain mitochondrial dysfunction, microglial dysmorphology, hippocampal dysplasticity, and increased apoptosis, resulting in cognitive decline. Ranolazine exerted neuroprotective effects by suppressing brain pathologies and restoring cognitive function. These findings suggest that ranolazine has a potential role in cardio- and neuro-protection against chemotherapy.
