Harsha V. Ganga

A systematic review of statin-induced muscle problems in clinical trials

Statin therapy is associated with muscle problems in approximately 10% to 25% of patients treated in clinical practice, but muscle problems have rarely been reported in controlled clinical trials. We performed a systematic search and review of statin clinical trials to examine how these studies evaluated muscle problems and to determine why there are apparent differences in muscle problems between clinical trials and practice. We initially identified 1,012 reports related to clinical trials of statin therapy, 42 of which qualified for analysis. Fifteen, 4, and 22 trials reported creatine kinase values only >10, 5, and 3 times the upper limits of normal, respectively, in both statin- and placebo-treated participants. Four trials reported average creatine kinase values, which increased with statin treatment in 3 instances. Twenty-six trials reported muscle problems, with an average incidence in statin- and placebo-treated participants of 13%, but only one trial specifically queried about muscle problems. Three trials used a run-in period to eliminate participants with statin intolerance and noncompliance. The percentage of muscle problems tended to be higher with statin treatment (12.7%) than with placebo group (12.4%, P = .06). This small difference probably reflects a high background rate of nonspecific muscle problems in both groups that could not be distinguished from statin-associated myalgia because most clinical trials did not use a standard definition for statin myalgia.

The impact of severe acidemia on neurologic outcome of cardiac arrest survivors undergoing therapeutic hypothermia

INTRODUCTION Therapeutic Hypothermia (TH) has become a standard of care in improving neurological outcomes in cardiac arrest (CA) survivors. Previous studies have defined severe acidemia as plasma pH<7.20. We investigated the influence of severe acidemia at the time of initiation of TH on neurological outcome in CA survivors. METHODS A retrospective analysis was performed on 196 consecutive CA survivors (out-of-hospital CA and in-hospital CA) who underwent TH with endovascular cooling between January 2007 and October 2012. Arterial blood gas drawn prior to initiation of TH was utilized to measure pH in all patients. Shockable and non-shockable CA patients were divided into two sub-groups based on pH (pH<7.2 and pH≥7.2). The primary end-point was measured using the Pittsburgh Cerebral Performance Category (CPC) scale prior to discharge from the hospital: good (CPC 1 and 2) and poor (CPC 3 to 5) neurologic outcome. RESULTS Sixty-two percent of shockable CA patients with pH≥7.20 had good neurological outcome as compared to 34% patients with pH<7.20. Shockable CA patients with pH≥7.20 were 3.3 times more likely to have better neurological outcome when compared to those with pH <7.20 [p=0.013, OR 3.3, 95% CI (1.28-8.45)]. In comparison, non-shockable CA patients with p≥7.20 did not have a significantly different neurological outcome as compared to those with pH<7.20 [p=0.97, OR 1.02, 95% CI (0.31-3.3)]. CONCLUSION Presence of severe acidemia at initiation of TH in shockable CA survivors is significantly associated with poor neurological outcomes. This effect was not observed in the non-shockable CA survivors.

Magnesium Adjunctive Therapy in Atrial Arrhythmias

Magnesium (Mg) is an important intracellular ion with cardiac metabolism and electrophysiologic properties. A large percentage of patients with arrhythmias have an intracellular Mg deficiency, which is out of line with serum Mg concentrations, and this may explain the rationale for Mgs benefits as an atrial antiarrhythmic agent. A current limitation of antiarrhythmic therapy is that the potential for cardiac risk offsets some of the benefits of therapy. Mg enhances the balance of benefits to harms by enhancing atrial antiarrhythmic efficacy and reducing antiarrhythmic proarrhythmia potential as well as providing direct antiarrhythmic efficacy when used as monotherapy in patients undergoing cardiothoracic surgery.

Risk of new-onset atrial fibrillation in elderly patients with the overlap syndrome: a retrospective cohort study.

Objective Co-existence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is referred to as overlap syndrome. Overlap patients have greater degree of hypoxia and pulmonary hypertension than patients with OSA or COPD alone. Studies showed that elderly patients with OSA alone do not have increased risk of atrial fibrillation (AF) but it is not known if overlap patients have higher risk of AF. To determine whether elderly patients with overlap syndrome have an increased risk of AF. Methods In this single center, community-based retrospective cohort analysis, data were collected on 2,873 patients > 65 years of age without AF, presenting in the year 2006. Patients were divided into OSA group (n = 60), COPD group (n = 416), overlap syndrome group (n = 28) and group with no OSA or COPD (n = 2369). The primary endpoint was incidence of new-onset AF over the following two years. Logistic regression was performed to adjust for heart failure (HF), coronary artery disease, hypertension (HTN), cerebrovascular disease, cardiac valve disorders, diabetes mellitus, hyperlipidemia, chronic kidney disease (CKD) and obesity. Results The incidence of AF was 10% in COPD group, 6% in OSA group and 21% in overlap syndrome group (P < 0.05). After adjusting for age, sex, HF, CKD, and HTN, patients with overlap syndrome demonstrated a significant association with new-onset AF (OR = 3.66, P = 0.007). HF, CKD and HTN were also significantly associated with new-onset AF (P < 0.05). Conclusion Among elderly patients, the presence of overlap syndrome is associated with a marked increase in risk of new-onset AF as compared to the presence of OSA or COPD alone.

Sports participation in non-compaction cardiomyopathy: a systematic review

Non-compaction cardiomyopathy (NCCM) is typified by deep invaginations of the myocardium and is caused by an arrest of normal myocardial morphogenesis. NCCM was once considered rare, but is now widely recognised owing to frequent use of advanced imaging techniques. NCCM can also be detected when competitive athletes undergo preparticipation screening for cardiac disease or when being evaluated for cardiac symptoms. It is not clear how athletes with NCCM should be managed. We searched PubMed and Google for articles addressing the issue of NCCM and athletic participation. We were able to identify only 18 cases of NCCM described in the context of sports, athletics or exercise. We conclude that there are insufficient data to develop firm recommendations on how to manage vigorous activity in patients with NCCM and future registries of sudden death in athletes should include a careful search for cases of NCCM among the victims so that clinicians can develop more definitive recommendations for athletes with this condition.

Supervised exercise training versus usual care in ambulatory patients with left ventricular assist devices: A systematic review

Implantation of left ventricular assist devices (LVAD) has increased because of improved safety profile and limited availability of heart transplantation. Although supervised exercise training (ET) programs are known to improve exercise capacity and quality of life (QoL) in heart failure (HF) patients, similar data is inconclusive in LVAD patients. Thus, we performed a systematic review on studies that incorporated supervised ET and measured peak oxygen uptake in LVAD patients. A total of 150 patients in exercise and 55 patients in control groups were included from 8 studies selected from our predefined criteria. Our systematic review suggests supervised ET has an inconsistent effect on exercise capacity and QoL when compared to control groups undergoing usual care. A quantitative sub-analysis was performed with 4 studies that provided enough data to compare peak oxygen uptake and QoL at baseline and at follow-up. After at least 6 weeks of training, LVAD patients undergoing supervised ET demonstrated significant improvement in exercise capacity (standardized mean difference [SMD] = 0.735, 95% Confidence Interval-[CI], 0.31–1.15 units of the standard deviation, P = 0.001) and QoL scores (SMD = 1.58, 95% CI 0.97–2.20 units of the standard deviation, P <0.001) when compared to the usual care group, with no serious adverse events with exercise. These results suggest that supervised ET is safe and can improve patient outcomes in LVAD patients when compared to the usual care.

Should Primary Prevention ICDs Still Be Placed in Patients with Non-ischemic Cardiomyopathy? A Review of the Evidence

Purpose of ReviewRecent evidence has suggested that implantable defibrillator (ICD) in non-ischemic cardiomyopathy (NICM) may not offer mortality benefit in the presence of guideline-directed medical therapy (GDMT) and cardiac resynchronization therapy (CRT).Recent FindingsDespite significant benefits of GDMT and CRT, current evidence is derived from ICD trials that rely predominantly on reduced left ventricular ejection fraction alone (LVEF). The majority of patients with sudden cardiac death (SCD) have LVEF > 30% indicating that LVEF by itself is an inadequate predictor of SCD. The Danish study to assess the efficacy of ICD in patients with non-ischemic systolic heart failure on mortality (DANISH) highlights the importance of better risk stratifying NICM patients for ICD implantation.SummaryAssessment of life expectancy, comorbidities, presence of advanced heart failure, etiology of NICM, and the presence of myocardial fibrosis can help risk stratify ICD beyond LVEF. Genetics and biomarkers can be of further assistance in risk stratification.