Role of metabolomics in identifying cardiac hypertrophy: an overview of the past 20 years of development and future perspective.

Cardiac hypertrophy (CH) is an augmentation of either the right ventricular or the left ventricular mass in order to compensate for the increase of work load on the heart. Metabolic abnormalities lead to histological changes of cardiac myocytes and turn into CH. The molecular mechanisms that lead to initiate CH have been of widespread concern, hence the development of the new field of research, metabolomics: one 'omics' approach that can reveal comprehensive information of the paradigm shift of metabolic pathways network in contrast to individual enzymatic reaction-based metabolites, have attempted and until now only 19 studies have been conducted using experimental animal and human specimens. Nuclear magnetic resonance spectroscopy and mass spectrometry-based metabolomics studies have found that CH is a metabolic disease and is mainly linked to the harmonic imbalance of glycolysis, citric acid cycle, amino acids and lipid metabolism. The current review will summarise the main outcomes of the above mentioned 19 studies that have expanded our understanding of the molecular mechanisms that may lead to CH and eventually to heart failure.

Hydropneumopericardium: A rare complication of pericardiocentesis.

Hydropneumopericardium is defined as the presence of air and water in the pericardial cavity. Several causes have been postulated which can lead to hydropneumopericardium including trauma, infections secondary to gas-producing bacilli, fistula formation, positive pressure ventilation or even spontaneously without an underlying cause in healthy adults and rarely after pericardiocentesis. We report an uncommon instance of hydropneumopericardium after pericardiocentesis in a 35-year-old man, which developed due to a leaky drainage system. It was immediately drained through the subxiphoid approach under echocardiographic guidance, and the patient was relieved. Hydropneumopericardium is an uncommon but easily diagnosable and avoidable complication of pericardiocentesis. It should be suspected whenever the patient develops increasing dyspnoea following a temporary relief by pericardiocentesis.

The time to reversal of complete atrioventricular block and its predictors in acute ST-segment elevation myocardial infarction.

OBJECTIVE: The purpose of this study was to determine the time to reversal of complete AV block (CAVB) in ST-segment elevation myocardial infarction (STEMI) with various modalities of treatment and to examine the factors associated with early reversal of CAVB. METHODS: We prospectively assessed the STEMI patients complicated by CAVB. The mean time to reversal of CAVB was analyzed and compared according to the treatment received. Multivariate logistic regression analysis was performed to find the predictors of mortality. RESULTS: Of 3954 patients with STEMI, CAVB was present in 146(3.7%) patients. Inferior wall myocardial infarction (IWMI) was more commonly associated with CAVB than anterior wall myocardial infarction (AWMI) (74.7% vs 25.3%). The mean time to reversal of CAVB was 25.4 ± 35.5 h. It was significantly lower with the primary percutaneous coronary intervention (PCI) compared to thrombolysis (5.21 ± 10.54 vs 12.98 ± 17.14; p = 0.0001). Predictors of early reversal of CAVB were early presentation to hospital (<6 h) from symptom onset, presence of IWMI, any revascularization done, primary PCI performed in comparison to thrombolysis, and normal serum creatinine levels. The presence of older age, broader QRS complex, cardiogenic shock/heart failure, and elevated creatinine were independent predictors of mortality. The CAVB reverted in all the alive patients except one who required permanent pacemaker implantation. CONCLUSION: CAVB is uncommon in STEMI and it recovers in a vast majority of surviving patients. The time to reversal of CAVB in STEMI is lower with primary PCI compared to thrombolysis. Outcomes are poor without revascularization in such patients.

An unusual case of isolated right-sided infective endocarditis masquerading as non-resolving pneumonia.

Right-sided infective endocarditis in non-intravenous drug abusers and non-immunocompromised patients is rare. The diagnosis is difficult as it can present as a respiratory illness leading to delays in diagnosis and development of complications, which can be fatal. The standard Duke criteria may not be adequate for diagnosis. We present a patient with isolated right-sided infective endocarditis mimicking right lower lobe non-resolving pneumonia who did not respond to antitubercular therapy.

Syndrome 'Z': A Predictor of Angiographic Severity of Coronary Artery Disease in Patients of Acute Coronary Syndrome.

BACKGROUND: Owing to the growing evidence that the pathophysiology of obstructive sleep apnoea (OSA) and metabolic syndrome (MS) overlap considerably and both adversely impact cardiovascular health, we hypothesised that the presence of OSA with MS additively and adversely affect the severity of coronary artery disease (CAD). Exploration and understanding of this may have direct implications for the development of targeted, preventive strategies for CAD. Thus, this prospective study was aimed to determine the prevalence of 'Syndrome Z' in patients of MS who present with an acute coronary event and to correlate it with the angiographic severity of CAD in these patients. METHODS: The present study was a single centre, cross sectional study conducted in a university teaching hospital. In a span of 6 months, 922 patients with acute coronary syndromes (ACS) were screened for the study. Among these, 861 patients had no evidence of MS. The remaining 61 patients who were diagnosed to have MS were then subjected to an overnight sleep study. Only 58 had good sleep data so were included for further analysis. Angiographic parameters in terms of number of vessels involved and culprit lesions were noted and correlated with presence and absence of OSA and also with its severity based on the Apnoea/Hypopnoea Index (AHI). RESULTS: The prevalence of OSA positivity in patients with MS who presented with ACS was 34.5% (n=20). Most of the patients in the OSA negative group (78.9%, n=30) had disease limited to only one vessel while in the OSA positive group only a minority (15%, n=3) of patients had their disease limited to a single vessel (p=0.001). The number of lesions in the culprit vessel was also significantly less in the OSA negative group compared to the OSA positive group. While in the OSA negative group 68.4% (n=26) patients had a solitary lesion, followed by two and three lesions in 15.8% (n=6) of the patients each, multiple lesions were more common in OSA positive patients, involving 80% of cases (45.0%, n=9 with two lesions; 35.0%, n=7 with three lesions; only 20%, n=4 had a solitary lesion). CONCLUSIONS: Prevalence of 'Syndrome Z' is high in patients having MS presenting with ACS and it correlates with the angiographic severity of CAD.

Obstructive Sleep Apnea and Cardiovascular Events After Percutaneous Coronary Intervention.

BACKGROUND: There is a paucity of data from large cohort studies examining the prognostic significance of obstructive sleep apnea (OSA) in patients with coronary artery disease. We hypothesized that OSA predicts subsequent major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing percutaneous coronary intervention. METHODS AND RESULTS: The Sleep and Stent Study was a prospective, multicenter registry of patients successfully treated with percutaneous coronary intervention in 5 countries. Between December 2011 and April 2014, 1748 eligible patients were prospectively enrolled. The 1311 patients who completed a sleep study within 7 days of percutaneous coronary intervention formed the cohort for this analysis. Drug-eluting stents were used in 80.1% and bioresorbable vascular scaffolds in 6.3% of the patients, and OSA, defined as an apnea-hypopnea index of ≥15 events per hour, was found in 45.3%. MACCEs, a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned revascularization, occurred in 141 patients during the median follow-up of 1.9 years (interquartile range, 0.8 years). The crude incidence of an MACCEs was higher in the OSA than the non-OSA group (3-year estimate, 18.9% versus 14.0%; p=0.001). Multivariate Cox regression analysis indicated that OSA was a predictor of MACCEs, with an adjusted hazard ratio of 1.57 (95% confidence interval, 1.10-2.24; P=0.013), independently of age, sex, ethnicity, body mass index, diabetes mellitus, and hypertension. CONCLUSIONS: OSA is independently associated with subsequent MACCEs in patients undergoing percutaneous coronary intervention. Evaluation of therapeutic approaches to mitigate OSA-associated risk is warranted. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01306526.

Effects of Ethnicity on the Prevalence of Obstructive Sleep Apnoea in Patients with Acute Coronary Syndrome: A Pooled Analysis of the ISAACC Trial and Sleep and Stent Study.

BACKGROUND: Obstructive sleep apnoea (OSA) is an emerging risk factor for acute coronary syndrome (ACS). We sought to determine the effects of ethnicity on the prevalence of OSA in patients presenting with ACS who participated in an overnight sleep study. METHODS: A pooled analysis using patient-level data from the ISAACC Trial and Sleep and Stent Study was performed. Using the same portable diagnostic device, OSA was defined as an apnoea-hypopnoea index of ≥15 events per hour. RESULTS: A total of 1961 patients were analysed, including Spanish (53.6%, n=1050), Chinese (25.5%, n=500), Indian (12.0%, n=235), Malay (6.1%, n=119), Brazilian (1.7%, n=34) and Burmese (1.2%, n=23) populations. Significant differences in body mass index (BMI) were found among the various ethnic groups, averaging from 25.3kg/m2 for Indians and 25.4kg/m2 for Chinese to 28.6kg/m2 for Spaniards. The prevalence of OSA was highest in the Spanish (63.1%), followed by the Chinese (50.2%), Malay (47.9%), Burmese (43.5%), Brazilian (41.2%), and Indian (36.1%) patients. The estimated odds ratio of BMI on OSA was highest in the Chinese population (1.17; 95% confidence interval: 1.10-1.24), but was not significant in the Spanish, Burmese or Brazilian populations. The area under the curve (AUC) for the Asian patients (ranging from 0.6365 to 0.6692) was higher than that for the Spanish patients (0.5161). CONCLUSION: There was significant ethnic variation in the prevalence of OSA in patients with ACS. The magnitude of the effect of BMI on OSA was greater in the Chinese population than in the Spanish patients.

Cardiac Output Assessment by Transthoracic Electrical Bio-impedance in Patients of Acute Myocardial Infarction: Comparative Analysis with Echocardiography.

Objectives: Transthoracic electrical bio-impedance (TEB) has been proposed as a non-invasive and continuous method of cardiac output (CO) measurement, but it still has not found wide usages in clinics. The present study measured CO, using a new instrument NICOMON, and compared it with Echocardiography (ECHO) in acute myocardial infarction (AMI) patients. Methods: In the present study 100 patients of AMI were assessed by both ECHO and NICOMON for cardiac output and ECHO is considered as a reference method for comparison. TEB CO was measured by passing an alternating current and measuring the bio-impedance across the thorax. End diastolic volume (EDV), End systolic volume (ESV) & Left ventricular outflow tract (LVOT) diameter, measured by ECHO were used to calculate CO. Various statistical methods like "t"-test & correlation coefficient (r) were used where found suitable. Results: Results: Mean TEB-CO (4.03±1.11 l/min) was significantly higher (p<0.001) than mean ECHO-CO (3.80±1.28 l/min) with a mean difference of 0.25±1.02 l/min. Conclusions: NICOMON measures CO non-invasively but, it needs more elaborative studies on a larger sample to establish it as an alternative method of ECHO for cardiac output measurement on regular basis.

Effect of Ivabradine on Heart Rate and Duration of Exercise in Patients With Mild-to-Moderate Mitral Stenosis: A Randomized Comparison With Metoprolol.

BACKGROUND: Symptoms in mitral stenosis (MS) are heart rate (HR) dependent. Increase in HR reduces diastolic filling period with rise in transmitral gradient. By reducing HR, beta-blockers improve hemodynamics and relieve symptoms, but the use may be limited by side effects. The present randomized crossover study looked at comparative efficacy of ivabradine and metoprolol on symptoms, hemodynamics, and exercise parameters in patients with mild-to-moderate MS (mitral valve area, 1-2 cm) in normal sinus rhythm. MATERIAL AND METHODS: Baseline clinical assessment, treadmill stress testing, and an echocardiographic Doppler evaluation were performed to determine resting HR, total exercise duration, mean gradient across mitral valve, and mean pulmonary artery systolic pressure (PASP). Patients were then allocated to either metoprolol or ivabradine to maximal tolerated doses over 6 weeks (metoprolol: 100 mg twice a day, ivabradine: 10 mg twice a day). Reevaluation was done at the end of this period, and all drugs stopped for washout over 2 weeks. Thereafter, the 2 groups were crossed over to the other drug that was continued for another 6 weeks. Assessment was again performed at the end of this period. RESULTS: Thirty-three patients of 34 completed the protocol. Fifteen were male, mean age was 28.9 ± 6.6 years, all were in New York Heart Association class 2, and mean resting HR was 103.5 ± 7.2/min. Mean mitral valve area was 1.56 ± 0.16 cm, mean PASP was 38.1 ± 5.1 mm Hg, and mean gradient across mitral valve was 10.6 ± 1.6 mm Hg. Significant decrease in baseline and peak exercise HR was observed at the end of follow-up with both drugs. Reduction in mitral valve gradient after ivabradine (42%) and metoprolol (37%) and reduction in PASP after both ivabradine (23%) and metoprolol (27%) were to a similar extent. Significant reduction in total exercise duration after both ivabradine and metoprolol therapy was observed. One patient developed blurring of vision with ivabradine therapy but did not require discontinuation of drug. An improvement in dyspnea of one grade was observed in all the patients by treatment with both ivabradine and metoprolol. CONCLUSIONS: Both metoprolol and ivabradine reduced symptoms and improved hemodynamics significantly from baseline to a similar extent. Ivabradine thus can be used effectively and safely in patients with MS in normal sinus rhythm who are intolerant or contraindicated for beta-blocker therapy.