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.

Ruptured anterior mitral leaflet aneurysm in aortic valve infective endocarditis--evaluation by three-dimensional echocardiography.

Ruptured aneurysm of the anterior mitral leaflet is a rare but a devastating complication secondary to aortic valve infective endocarditis. We report a case of 30-year-old male with native aortic valve endocarditis who was referred to us for evaluation of worsening of heart failure after an initial period of responsiveness to antibiotics. Detailed evaluation with two-dimensional and three-dimensional transthoracic echocardiography revealed ruptured anterior mitral leaflet aneurysm with severe eccentric mitral regurgitation along with a large vegetation on the aortic valve. The patient underwent successful surgical closure of the defect along with aortic valve replacement.

Multimodality imaging of submitral left ventricular aneurysm.

Submitral left ventricular aneurysms are a rare nonischemic aneurysm thought to be developmental in origin. These aneurysms invariably occur at the site of posterior mitral annulus and lead to mitral valve incompetence. We hereby describe a case of a 30-year-old adult with a rare form of submitral left ventricular aneurysm involving whole of the posterior mitral annulus. Multimodality imaging with two-dimensional echocardiography, three-dimensional echocardiography, computed tomography and invasive left ventriculography helped the patient to undergo successful resection of the aneurysm along with mitral valve replacement.

Clopidogrel resistance and its relevance: Current concepts.

Clopidogrel is the most widely used P2Y12 receptor inhibitor (P2Y12i) as a part of dual antiplatelet therapy along with aspirin. Clopidogrel is a pro-drug and is metabolized to its active metabolite by the hepatic enzyme cytochrome P4502C19 (CYP2C19). This active metabolite is responsible for the antiplatelet action of clopidogrel. Recent studies have demonstrated that single nucleotide polymorphisms in the CYP2C19 gene, including CYP2C19*2,*3,*4, and *5 alleles, result in reduced production of the active metabolite of clopidogrel, and hence reduced inhibition of platelet aggregation. This in turn enhances the incidence of stent thrombosis and recurrent cardiovascular (CV) events. We report a case of coronary stent thrombosis due to clopidogrel resistance proven by CYP2C19 genotyping. We then review the literature on clopidogrel resistance and its impact on CV outcomes. Subsequently, we discuss the methods of diagnosis of resistance, evidence from clinical trials for tailoring clopidogrel therapy, the role of potent P2Y12 inhibitors, the current guidelines, and future directions.

Cor Triatriatum Dexter with Noncompaction of Right Ventricle and Complete Heart Block: An Unholy Trinity.

Cor triatriatum (CT) or a triatrial heart is a rare congenital anomaly in which one of the atrial chambers is divided by a fibromuscular membrane. Of the two variants, CT dexter (right-sided CT) is still further rare than CT sinister (left-sided CT). Although CT sinister presents with features of left heart obstructive disease mimicking mitral stenosis, CT dexter is usually asymptomatic and is found incidentally on imaging. Here, we present a patient with an unusual case of complete heart block who was found to have CT dexter along with right ventricular noncompaction on imaging.

Sinus Node Dysfunction and Pulmonary Hypertension-"Double Trouble" with Lithium Therapy.

Lithium is considered a gold standard drug for the management of bipolar disorder and is a widely used mood-stabilizing drug in psychiatry practice. However, its side effects are of important concern. The narrow therapeutic index of lithium predispose to its toxicity/side effects, but various case reports and research has shown that adverse drug reactions can occur even in the therapeutic range. We present the case of a 56-year-old woman with no history of cardiac illness presenting with tachycardia-bradycardia syndrome along with moderate pulmonary hypertension. Patients recovered to sinus rhythm after withholding lithium therapy for 1 week while her mean pulmonary artery pressure remained the same at day 10 of drug withdrawal.

Comparative analysis of central aortic blood pressure, pulse wave velocity & arterial stiffness in patients with obstructive airway disease.

BACKGROUND: As the pulmonary system and cardiovascular system are intimately linked, patients with chronic obstructive pulmonary disease (COPD) and asthma have high risk for developing cardiovascular diseases (CVDs) and altered central hemodynamic. OBJECTIVE: We aim to assess the central aortic blood pressure (CABP) indices, pulse wave velocity (PWV) and other indicators of arterial stiffness in Indian patients with COPD and bronchial asthma. METHODS: This is a single-center, cross-sectional study conducted in outpatients diagnosed with either chronic stable phase of COPD or bronchial asthma. CABP indices, vascular age, arterial stiffness and central hemodynamics were measured in patients. RESULTS: Of 193 patients with obstructive airway disease who were enrolled, (n = 81 had COPD and n = 112 had partially-controlled bronchial asthma) the proportion of male patients was higher in both groups. The PWV, augmentation index (AI) and vascular age (VA) were significantly higher in patients with COPD compared to those with bronchial asthma (all, p < 0.05). CONCLUSION: The study showed that PWV, AI and VA were higher in patients with stable COPD without any cardiac comorbidities compared to bronchial asthma.

The unpredictable resorption of bioresorbable scaffolds-A tale of two ABSORBs.

Bioresorbable stents represent a revolutionary treatment for coronary artery disease. Such a device offers the prospect for complete naturalization of artery lumen after strut resorption and restoration of vasomotion while curtailing the duration of dual anti-platelet therapy. The prototype bioresorbable scaffold (BRS-ABSORB GT1) demonstrated good feasibility and safety in the initial studies compared to metallic drug eluting stent but later fell out of favor due to multiple report of stent thrombosis and target lesion failure. Unpredictable resorption of struts turned out to be one of the "Achilles heel" of the BRS and stent strut were still visible in vessel on optical coherence tomography (OCT) at 3 years. We report a case of differential resorption of two ABSORB BRS implanted simultaneously in the same patient by the same operator. Follow up coronary angiogram revealed only minimal plaques on right coronary artery (RCA) and left anterior descending artery (LAD). The BRS were identified on cine-angiogram by their radio-opaque markers at both ends. The OCT run in LAD artery revealed "ghost remnants" of BRS struts in LAD, whereas the RCA BRS had completely healed with minimal "ghost" struts. The ghost remnants of BRS resembled the original "Check box" appearance on OCT during the index implantation.

Reliability of Fractional Flow Reserve in Non-Infarct-Related Arteries in ST-Segment Elevation Myocardial Infarction Patients Undergoing a Pharmaco-Invasive Approach.

Objectives We investigated the reproducibility of fractional flow reserve (FFR) of significant stenoses (≥70% narrowing) in the non-infarct related artery (NIRA) during the pharmaco-invasive percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) within 24 hours of thrombolysis and at a follow up of 2-3 weeks. Background STEMI with multivessel disease has worse outcomes. The benefits of FFR-directed PCI of NIRA at the time of primary PCI are yet controversial. Assessing the hemodynamic severity of the NIRA may help in deciding the management strategy of these lesions, save time, and avoid complications. Methods Thirty-one patients undergoing PCI for STEMI under a pharmaco-invasive approach were prospectively recruited. The FFR measurements in 34 stenoses (≥70% diameter stenosis) were obtained immediately after PCI of the culprit stenosis and were repeated at a mean follow-up of 17.6 ± 3.55 (14-21) days. In addition, time to thrombolysis, time from symptom onset to PCI, left ventricular ejection fraction (LVEF), quantitative coronary angiographic measurements of the non-culprit stenoses, and thrombolysis in myocardial infarction (TIMI) flow were recorded. Results There was a significant change in FFR values at follow-up as compared to baseline (0.78 ± 0.08 (0.68-0.93) to 0.77 ± 0.08 (0.67-0.93)) (p = 0.014). In four of the lesions, the FFR values differed by >0.05 at follow-up. The follow-up FFR values led to a change in the management strategy in 5 out of 31 patients (15%) of the lesions. The TIMI flow, percentage diameter stenosis, minimum lumen diameter, and LVEF did not change. There were no predictors of this change in FFR values. Conclusions During the acute phase of STEMI, the severity of non-culprit coronary artery stenoses can not be reliably assessed by FFR. The prolonged jeopardized state of myocardium in pharmaco-invasive PCI as compared to primary PCI seems to be responsible.

Differential culprit plaque morphology in acute coronary syndrome: a comparison between very young patients (≤35 years) and older counterparts using optical coherence tomography.

Aims: Underlying mechanisms responsible for acute coronary syndrome (ACS) in young patients compared with older counterparts are yet to be explored with optical coherence tomography (OCT). This study aims to explore underlying mechanisms of ACS in ≤35- (very young) and >35-year-old (older counterparts) ACS patients using OCT. Methods and results: This was a prospective, single-centre, investigational study. Patients were divided into groups according to age (≤35 and >35 years) and further subdivided according to the underlying mechanism i.e. plaque rupture (PR) and plaque erosion (PE). A total of 93 patients were analysed. Thin-cap fibroatheroma (TCFA) was significantly higher among older counterparts than very young patients for both PR (80.0% vs. 31.8%, P = 0.002) and PE (66.7% vs. 6.3%, P < 0.001) groups. Microchannels were also significantly more prevalent among older than very young patients for both PR (65.0% vs. 18.2%, P = 0.004) and PE groups (55.6% vs.12.5%, P = 0.013). Macrophages were significantly higher in older than very young patients for both PR (25.0% vs. 0%, P = 0.018) and PE (44.4% vs. 0%, P = 0.003) groups. In contrast, fibrous cap thickness was greater in very young than older patients for both PR (105.71 ± 48.02 vs. 58.00 ± 15.76 µm, P < 0.001) and PE (126.67 ± 48.22 vs. 54.38 ± 24.21 µm, P < 0.001) groups. Intimal thickness was greater in older than very young patients for both PR (728.00 ± 313.92 vs. 342.27 ± 142.02 µm, P < 0.001) and PE (672.78 ± 334.57 vs. 295.00 ± 99.60 µm, P < 0.001) groups. Conclusion: Frequency of TCFA, microchannels, macrophages, and intimal thickness was significantly higher in older ACS patients compared with very young patients. However, fibrous cap thickness was significantly greater in very young ACS patients compared with older patients.