Anti-ischemic and pleiotropic effects of ranolazine in chronic coronary syndromes.

The vast majority of antianginal drugs decrease heart rate and or blood pressure levels or the inotropic status of the left ventricle to decrease myocardial oxygen consumption (MVO2) and thus anginal symptoms. Ranolazine presents a completely different mechanism of action, which reduces the sodium-dependent calcium overload inhibiting the late sodium current. Current European Society of Cardiology (ESC) guidelines for the management of angina in patients with chronic coronary symptoms recommend the use of several drugs such as ranolazine, b-blockers, calcium channel blockers, long-acting nitrates, ivabradine, nicorandil and trimetazidine for angina relief. However, ranolazine, in addition to symptom relief properties, is an antianginal drug showing favorable effects in decreasing the arrhythmic burden and in ameliorating the glycemic profile of these patients. In this review, we summarize the available data regarding the antianginal and pleiotropic effects of this drug.

One-Year Outcomes in Anticoagulated Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention: Insights From the Greek Antiplatelet Atrial Fibrillation Registry.

ABSTRACT: GReek-AntiPlatElet Atrial Fibrillation registry is a multicenter, observational, noninterventional study of atrial fibrillation patients undergoing percutaneous coronary intervention. Primary endpoint included clinically significant bleeding rate at 12 months between different antithrombotic regimens prescribed at discharge; secondary endpoints included major adverse cardiovascular events and net adverse clinical events. A total of 647 patients were analyzed. Most (92.9%) were discharged on novel oral anticoagulants with only 7.1% receiving the vitamin K antagonist. A little over half of patients (50.4%) received triple antithrombotic therapy (TAT)-mostly (62.9%) for ≤1 month-whereas the rest (49.6%) received dual antithrombotic therapy (DAT). Clinically significant bleeding risk was similar between TAT and DAT [Hazard ratio (HR) = 1.08; 95% confidence interval (CI), 0.66-1.78], although among TAT-receiving patients, the risk was lower in those receiving TAT for ≤1 month (HR = 0.50; 95% CI, 0.25-0.99). Anticoagulant choice (novel oral anticoagulant vs. vitamin K antagonist) did not significantly affect bleeding rates ( P = 0.258). Age, heart failure, leukemia/myelodysplasia, and acute coronary syndrome were associated with increased bleeding rates. Risk of major adverse cardiovascular events and net adverse clinical events was similar between ΤAT and DAT (HR = 1.73; 95% CI, 0.95-3.18, P = 0.075 and HR = 1.39; 95% CI, 0.93-2.08, P = 0.106, respectively). In conclusion, clinically significant bleeding and ischemic rates were similar between DAT and TAT, although TAT >1 month was associated with higher bleeding risk.

Effects of ranolazine on various outcomes in patients with stable angina: an updated meta-analysis.

OBJECTIVE: We determined the effect of ranolazine vs. placebo in angina patients on 1) selective measures of the ischemic burden, 2) cardiovascular outcomes, including atrial fibrillation incidence, 3) the in-treatment glycohemoglobin levels and the permanent discontinuations because of side effects, and 4) the achieved between-arms blood pressure and heart rate difference. METHODS: PubMed and Cochrane Collaboration Library databases were searched for eligible trials until end of September 2020. Trial quality was assessed by the Rob2 tool. Risk ratios or achieved mean differences during follow-up and 95% confidence interval (CI) of categorical or continuous outcomes, respectively, were calculated (random-effects model). The relationship between discontinuation rates and ranolazine's mean dose was investigated by meta-regression analysis. RESULTS: We selected 18 trials (n = 12,995 patients in patients with macro or microvascular coronary heart disease. Achieved blood pressure and heart rate at rest were not different between randomized arms. Ranolazine administration compared to placebo was associated with an increase of 1) total exercise duration by 30 seconds (95% CI, 18-42), 2) time to 1 mm ST-segment depression by 44 seconds (95% CI, 30-54), and 3) time to angina onset by 40 seconds (95% CI, 30-54). On average, the incidence of atrial fibrillation was reduced by 25% following ranolazine treatment compared to placebo, while glycohemoglobin showed a mean decrease of 0.4% (95% CI, 0.3-0.5%). DISCUSSION: Ranolazine remains an effective anti-ischemic drug, increases the angina-free exercise duration, delays the onset of ST-segment depression. The beneficial effects of ranolazine are extended to atrial fibrillation reduction rates and better glycemic control.

Angiographic predictors of aberrant circumflex artery during cardiac catheterization.

OBJECTIVES: To identify angiographic predictors of aberrant left circumflex artery (LCx) by comparing left main (LM) length and bifurcation angle between patients with aberrant LCx and normal anatomy. BACKGROUND: Failure to recognize aberrant LCx during a cardiac catheterization may hamper correct diagnosis, delay intervention in acute coronary syndromes, and result in increased contrast volume, radiation exposure, and infarct size. METHODS: We retrospectively analyzed angiograms of aberrant LCx patients and normal anatomy matched controls, in three-participating centers. LM-length, bifurcation angle between the left anterior descending (LAD) and the first non-LAD branch of the LM, and procedural data were compared. RESULTS: Between 2003 and 2020, 136 patients with aberrant LCx and 135 controls were identified. More catheters (2.4 ± 0.6 vs. 2.2 ± 0.9, p = 0.009), larger contrast volumes (169 ± 94 ml vs. 129 ± 68 ml, p < 0.0005), and prolonged fluoroscopy time (652.9 ± 623.7 s vs. 393.1 ± 332.1 s, p < 0.0005), were required in the aberrant LCx-group compared with controls. Patients with aberrant LCx had a longer LM-length and a more acute bifurcation angle, both in caudal and cranial views, compared with controls (24.7 ± 8.1 vs. 10.8 ± 4.5 mm, p < 0.0005 and 26.7 ± 7.4 vs. 12 ± 5.5 mm, p < 0.0005, respectively, and 45.2° ± 12° vs. 88.8° ± 23°, p < 0.0005 and 51.9° ± 21° vs. 68.2° ± 28.3°, p < 0.0005, respectively). In ROC analysis, LM-length showed the best diagnostic accuracy for detecting aberrant LCx. In multiple logistic regression analysis, a cranially measured LM-length > 17.7 mm was associated with a 5.3 times greater probability of predicting aberrant LCx [95% CI (3.4-8.1), p < 0.0001]. CONCLUSIONS: Our study suggests that a long LM-length and an acute bifurcation angle can indicate the presence of aberrant LCx. We present a practical algorithm for its rapid identification.

Verapamil-sensitive idiopathic left ventricular tachycardia and concomitant atrioventricular nodal reentrant tachycardia.

We describe the case of a young patient with runs of repetitive monomorphic left ventricular tachycardia. He was diagnosed with verapamil-sensitive, idiopathic left ventricular tachycardia (ILVT) and underwent an electrophysiological study, in which dual atrioventricular (AV) nodal physiology was evident, with an AV nodal reentrant tachycardia (AVNRT) being easily and reproducibly induced. Both the AVNRT and the ILVT were successfully ablated using high-density electroanatomical mapping and an open-irrigation catheter. In conclusion, verapamil-sensitive ILVT might coexist with AVNRT. In case of invasive therapy, a thorough electrophysiological evaluation is mandatory to exclude or treat other co-existing reentrant supraventricular arrhythmias.

Joint ESH excellence centers' national meeting on renal sympathetic denervation: A Greek experts' survey.

OBJECTIVE: The efficacy of renal sympathetic denervation (RDN) has been affirmed by a number of recent clinical studies, despite controversies in this field over the last five years. Therefore, it is of paramount importance that hypertension experts debate the merits of RDN by revealing and expressing their personal beliefs and perspectives regarding this procedure. METHODS: A cross-sectional survey was conducted among Greek leaders of the Hypertension Excellence Centers with the use of a closed-type questionnaire specifically designed to elicit information and evaluate the respondent's views and perspectives about RDN efficacy, safety and ideal target patient population. RESULTS: A total of 36 participants completed the survey. Based on the results, RDN was considered efficient (91.7%) and safe (94.5%), while the overwhelming majority of the participants felt confident in the long-term efficacy (88.9%) of the intervention and that it lacks reliable predictors of blood pressure response (94.5%). Patients with resistant (91.7%), ultra-resistant (94.4%), and uncontrolled hypertension (80.6%) were suggested as ideal candidates for RDN. Establishing a close co-operation between interventionalists and hypertension experts was considered essential to ensure the efficacy (97.2%) as well as the safety (97.3%) of the procedure. CONCLUSION: The vast majority of Greek hypertension experts surveyed were convinced of the efficacy and safety of RDN based on the preponderance of available scientific and clinical data. Identification of the ideal patient group remains controversial. Respondents generally agreed on the necessity of building close collaborative relationships between interventionalists and hypertension experts in order to improve RDN clinical outcome.

Should Percutaneous Coronary Intervention be the Standard Treatment Strategy for Significant Coronary Artery Disease in all Octogenarians?

Coronary artery disease (CAD) remains the leading cause of cardiovascular death in octogenarians. This group of patients represents nearly a fifth of all patients treated with percutaneous coronary intervention (PCI) in real-world practice. Octogenarians have multiple risk factors for CAD and often greater myocardial ischemia than younger counterparts, with a potential of an increased benefit from myocardial revascularization. Despite this, octogenarians are routinely under- -treated and belittled in clinical trials. Age does make a difference to PCI outcomes in older people, but it is never the sole arbiter of any clinical decision, whether in relation to the heart or any other aspect of health. The decision when to perform revascularization in elderly patients and especially in octogenarians is complex and should consider the patient on an individual basis, with clarification of the goals of the therapy and the relative risks and benefits of performing the procedure. In ST-segment elevation myocardial infarction (MI), there is no upper age limit regarding urgent reperfusion and primary PCI must be the standard of care. In non-ST-segment elevation acute coronary syndromes, a strict conservative strategy must be avoided; whereas the use of a routine invasive strategy may reduce the occurrence of MI and the need for revascularization at follow-up, with no established benefit in terms of mortality. In stable CAD patients, invasive therapy on top of optimal medical therapy seems better in symptom relief and quality of life. This review summarizes the available data on percutaneous revascularization in the elderly patients and particularly in octogenarians, including practical considerations on PCI risk secondary to ageing physiology. We also analyse technical difficulties met when considering PCI in this cohort and the ongoing need for further studies to ameliorate risk stratification and eventually outcomes in these challenging patients.

[Case Report] Stress induced (Takotsubo) cardiomyopathy triggered by the COVID-19 pandemic.

Stress induced (Takotsubo) cardiomyopathy (TC) represents an acute heart failure syndrome triggered by physical or emotional stressors. COVID-19 pandemic has caused an unprecedented health crisis resulting in fear, distress and anxiety, with emerging cardiovascular implications. COVID-19 related stress can act as potential trigger for TC. We present a case of an elderly female who developed TC due to stress surrounding COVID-19.

Cardiac arrhythmias in arterial hypertension.

Patients with arterial hypertension frequently manifest various cardiac rhythm disturbances, ranging from bradyarrhythmias to supraventricular premature beats, atrial fibrillation, or other supraventricular and ventricular tachyarrhythmias. These cardiac arrhythmias may either cause symptoms or be completely asymptomatic, depending on the underlying cardiac function. Degenerative electrical disease and left ventricular hypertrophy constitute the principal pathophysiological mechanisms. This review summarizes all important existing evidence on cardiac arrhythmia manifestation in the setting of arterial hypertension, and it highlights known underlying pathophysiological mechanisms and therapeutic considerations.

The effect of Mid-Day Sleep on blood pressure levels in patients with arterial hypertension.

STUDY OBJECTIVES: Lifestyle changes decrease blood pressure (BP) levels by 3-5 mmHg in hypertensive patients. We assessed the effect of mid-day sleep on BP levels in hypertensive patients. METHODS: We prospectively studied two hundred and twelve hypertensive patients. Mid-day sleep duration, lifestyle habits, anthropometric characteristics, office BP, ambulatory BP monitoring, pulse wave velocity (PWV), augmentation index (AI) were recorded. A standard echocardiographic evaluation was performed. RESULTS: 53.8% were females, mean age was 62.5±11.0 years and mean body mass index was 28.9±5.4kg/m2. Mean average 24h systolic and diastolic BP (SBP & DBP) was 129.9±13.2/76.7±7.9 mmHg respectively. The majority was non-smokers (70.3%) and did not have diabetes (74.7%). The mean midday sleep duration was 48.7±54.3 min. Average 24h SBP (127.6±12.9 mmHg vs 132.9±13.1 mmHg), average daytime SBP & DBP were lower in patients who sleep at midday, compared to those who do not (128.7±13/76.2±11.5 vs 134.5±13.4/79.5±10.4 mmHg) (p<0.005). The effect was not correlated to the dipping status. Midday sleep duration was negatively correlated with average 24h SBP & daytime SBP. In a linear regression model, for every 60 min of midday sleep, 24h average SBP decreases by 3 mmHg (p<0.001). There were no differences in the number of antihypertensive medications, PWV, AI or echocardiographic indices between study groups. CONCLUSIONS: Mid-day sleep significantly decreases average 24h and daytime SBP/DBP in hypertensives. Its effect seems to be as potent as other well-established lifestyle changes and is independent of dipping status.

Optimal Treatment Strategy for Coronary Artery Stenoses with Grey Zone Fractional Flow Reserve Values. A Systematic Review and Meta-Analysis.

OBJECTIVES: We conducted a review and meta-analysis of published data to compare revascularization to deferral strategy for coronary lesions with grey zone fractional flow reserve (FFR). BACKGROUND: Optimal treatment for coronary stenoses with FFR values between 0.75 and 0.80, the so-called grey zone, remains a matter of debate. METHODS: We included all studies evaluating revascularization versus deferral for lesions with grey zone FFR. The primary outcome was study-defined major adverse cardiac events (MACE). Secondary outcomes were the composite of death or MI and target vessel revascularization (TVR). A total of 2362 patients were included, of whom 1181 underwent revascularization (revascularization group) and 1181 received medical treatment only (deferral group). RESULTS: After a mean follow-up period of 2.4 years, no difference was found for the primary outcome of the study-defined MACE between the two groups [RR = 1.33 (0.73-2.44), p = 0.35]. In addition, there was no difference for the secondary outcomes of death or MI and TVR between the two groups [RR = 1.39 (0.56-3.47), p = 0.48 and RR = 1.49 (0.89-2.51), p = 0.13, respectively]. CONCLUSIONS: In this meta-analysis revascularization of coronary stenoses with grey zone FFR showed no advantage over a deferral strategy in terms of study-defined MACE. Case by case judgment should be implemented to guide treatment in this special subset of patients.

Evaluation, risk stratification and management of hypertensive patients in the perioperative period.

Uncontrolled hypertension represents an important cause for postponing a non-cardiac surgery. Perioperative management of hypertensive patients should focus on cardiovascular risk stratification, evaluation of blood pressure levels and hypertension control, registration of the ongoing antihypertensive regimen and counseling about clinical decisions related to the expected perioperative blood pressure fluctuations. To date, there is a lack of evidence on how hypertensive patients should be perioperatively treated, while an empirical clinical approach is usually pursued in the usual practice. The present review appraises the gaps in the evidence and illustrates the current empirical approach of perioperative management of hypertension in non-cardiac surgery.

Practical Recommendations for the Diagnosis and Medical Management of Stable Angina: An Expert Panel Consensus.

Stable angina affects a significant number of coronary artery disease patients, impairing their quality of life and worsening their prognosis. It manifests even despite a history of revascularization and is often poorly controlled with drug therapy. Comorbid conditions are frequently encountered in coronary artery disease patients, affecting their prognosis and rendering the diagnosis and management of angina more challenging. In this article, derived by an expert panel meeting, we attempt a practical approach to stable angina, focusing on symptomatic patients subjected to previous coronary revascularization or not suitable for revascularization and providing handy diagnostic and therapeutic algorithms and comorbidity-adjusted therapeutic approaches in accordance with existing evidence, current recommendations, and locally available therapeutic options.

Perioperative SBP changes during orthopedic surgery in the elderly: clinical implications.

OBJECTIVES: We aimed to determine SBP changes during the perioperative period of a scheduled knee surgery under regional anesthesia and the extent of perioperative (in-hospital) white-coat effect. METHODS: All patients (aged ≥60 years) underwent clinic SBP measurements during both cardiological and anesthesiological visits, while home SBP the week before admission was obtained. Clinic SBP was registered just before surgery, during surgery and reanimation. Ambulatory monitoring was also performed (12 h before surgery to 6-8 h after surgery). One month after discharge, clinic SBP was measured at hypertension unit. RESULTS: Eligible participants (N = 50, mean age 74 ±â€Š7 years, 34% men, 26% with history of cardiovascular disease) had higher SBP during the anesthesiologic than the cardiological evaluation (157 ±â€Š23 vs. 144 ±â€Š18 mmHg, P < 0.001), and the former levels were almost identical to those clinically measured just before surgery. A significant white-coat effect between ambulatory and clinic measurements just before surgery (16.4 ±â€Š21 mmHg, P < 0.001) and between entire ambulatory recording and clinic BP measurements the day before surgery (12.4 ±â€Š16 and 24.8 ±â€Š21 mmHg for cardiologic and anesthesiologic visit, respectively, P < 0.001 for both) was noticed, whereas intraoperatively the white-coat effect faded away. There was a greater SBP decline during surgery in patients aged more than 75 years compared with younger, whereas selective treatment discontinuation (except beta blockers and calcium channel blockers) did not modulate SBP trajectories. CONCLUSION: The significant white-coat effect observed in scheduled noncardiac surgery is clinically important and the home BP measurement performed before surgery or ABPM, highly reflects the hypertensive burden of the patient. Blood pressure decrease during surgery is quite pronounced especially in patients aged more than 75 years. Aggressive BP lowering should be avoided.

Trimetazidine in the Prevention of Tissue Ischemic Conditions.

Trimetazidine (TMZ) is a metabolic agent with significant anti-ischemic properties. By inhibiting the terminal enzyme in the ß-oxidation pathway, it shifts the energy substrate metabolism, enhancing glucose metabolism. Thus, it maintains the required energy production with less oxygen consumption, an effect necessary in cases of myocardi. Trimetazidine was recently reaccredited as add-on therapy for symptomatic treatment in patients with stable angina, not adequately controlled or intolerant to first-line therapy. Trimetazidine was included in the European Society of Cardioloy 2013 guidelines for the management of stable coronary artery disease. Although TMZ has been used in cardiology for >40 years, only a few studies have assessed its effects in patients with acute ischemic conditions. This review summarizes the current literature regarding the addition of TMZ in patients with acute ischemic conditions (acute myocardial infarction, ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting). There is growing evidence from recent studies that the addition of TMZ in patients with such conditions is beneficial in terms of myocardial damage and major cardiac events as well as decreasing reperfusion injury and contrast-induced nephropathy.