Sanoj Chacko

A meta‐analysis of the prognostic significance of atrial fibrillation in chronic heart failure

Atrial fibrillation (AF) is one of the commonest sustained arrhythmias in chronic heart failure (CHF), although the prognostic implications of the presence of AF in CHF remain controversial. We have therefore performed this meta‐analysis to study the effects of the presence of AF on mortality in CHF patients.

Activation of Pak1/Akt/eNOS signaling following sphingosine-1-phosphate release as part of a mechanism protecting cardiomyocytes against ischemic cell injury.

We investigated whether plasma long-chain sphingoid base (LCSB) concentrations are altered by transient cardiac ischemia during percutaneous coronary intervention (PCI) in humans and examined the signaling through the sphingosine-1-phosphate (S1P) cascade as a mechanism underlying the S1P cardioprotective effect in cardiac myocytes. Venous samples were collected from either the coronary sinus (n = 7) or femoral vein (n = 24) of 31 patients at 1 and 5 min and 12 h, following induction of transient myocardial ischemia during elective PCI. Coronary sinus levels of LCSB were increased by 1,072% at 1 min and 941% at 5 min (n = 7), while peripheral blood levels of LCSB were increased by 579% at 1 min, 617% at 5 min, and 436% at 12 h (n = 24). In cultured cardiac myocytes, S1P, sphingosine (SPH), and FTY720, a sphingolipid drug candidate, showed protective effects against CoCl induced hypoxia/ischemic cell injury by reducing lactate dehydrogenase activity. Twenty-five nanomolars of FTY720 significantly increased phospho-Pak1 and phospho-Akt levels by 56 and 65.6% in cells treated with this drug for 15 min. Further experiments demonstrated that FTY720 triggered nitric oxide release from cardiac myocytes is through pertussis toxin-sensitive phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase signaling. In ex vivo hearts, ischemic preconditioning was cardioprotective in wild-type control mice (Pak1f/f), but this protection appeared to be ineffective in cardiomyocyte-specific Pak1 knockout (Pak1cko) hearts. The present study provides the first direct evidence of the behavior of plasma sphingolipids following transient cardiac ischemia with dramatic and early increases in LCSB in humans. We also demonstrated that S1P, SPH, and FTY720 have protective effects against hypoxic/ischemic cell injury, likely a Pak1/Akt1 signaling cascade and nitric oxide release. Further study on a mouse model of cardiac specific deletion of Pak1 demonstrates a crucial role of Pak1 in cardiac protection against ischemia/reperfusion injury.

Serum sphingolipids level as a novel potential marker for early detection of human myocardial ischaemic injury.

Background: Ventricular tachyarrhythmias are the most common and often the first manifestation of coronary heart disease and lead to sudden cardiac death (SCD). Early detection/identification of acute myocardial ischaemic injury at risk for malignant ventricular arrhythmias in patients remains an unmet medical need. In the present study, we examined the sphingolipids level after transient cardiac ischaemia following temporary coronary artery occlusion during percutaneous coronary intervention (PCI) in patients and determined the role of sphingolipids level as a novel marker for early detection of human myocardial ischaemic injury. Methods and Results: Venous samples were collected from either the coronary sinus (n = 7) or femoral vein (n = 24) from 31 patients aged 40–73 years-old at 1, 5 min, and 12 h, following elective PCI. Plasma sphingolipids levels were assessed by HPLC. At 1 min coronary sinus levels of sphingosine 1-phosphate (S1P), sphingosine (SPH), and sphinganine (SA) were increased by 314, 115, and 614%, respectively (n = 7), while peripheral blood levels increased by 79, 68, and 272% (n = 24). By 5 min, coronary sinus S1P and SPH levels increased further (720%, 117%), as did peripheral levels of S1P alone (792%). Where troponin T was detectable at 12 h (10 of 31), a strong correlation was found with peak S1P (R2 = 0.818; P < 0.0001). Conclusion: For the first time, we demonstrate the behavior of plasma sphingolipids following transient cardiac ischaemia in humans. The observation supports the important role of sphingolipids level as a potential novel marker of transient or prolonged myocardial ischaemia.

Prognostic value of demographic factors, pre-test probability scoring, exercise test diagnosis, and inability to exercise in patients with recent onset suspected cardiac chest pain

Aims: To assess the prognostic value of an inconclusive exercise test or inability to exercise in patients with recent onset suspected cardiac chest pain and to determine the independent predictors of events in these patients. Methods: This was an observational follow-up study of patients presenting to a rapid access chest pain clinic with a history of recent-onset suspected cardiac chest pain as referred by the family practitioner. The main outcome measure was a composite endpoint of death and acute coronary syndrome hospital admission. Results: The study cohort consisted of 1851 patients in whom a total of 147 events were recorded during a mean follow-up period of 4.1 ± 1.1 years. Those with events were significantly older (65.1 ± 12.5 years versus 56.4 ± 13.2 years, p < 0.001), had higher mean pre-test probability of coronary artery disease (CAD), and had higher prevalence of diabetes (18.4% vs. 13.6%, p < 0.001), hypertension (55.8% vs. 38.7%, p < 0.001), and smoking (36.7% vs. 25.4%, p = 0.03) than those without events. These patients were also more likely to have a positive exercise electrocardiogram (ECG) (15.6% vs. 8.6%, p < 0.001) or not have a diagnostic exercise test because of an inconclusive result or inability to exercise (60.5% vs. 28.6%, p < 0.001). Cox multivariate regression analysis showed that age (hazard ratio, HR 1.03, p < 0.001), pre-test probability of CAD (HR 1.08, p = 0.04), positive exercise ECG (HR 2.94, p < 0.001), and an inconclusive test or inability to exercise (HR 3.45, p < 0.001) were independent predictors of events. Conclusions: In patients with recent onset suspected cardiac chest pain, not having a diagnostic exercise ECG because of an inconclusive test or inability to exercise is an independent predictor of events and has similar prognostic implications to a positive exercise ECG. In addition, pre-test probability estimation at baseline is a robust indicator of clinical outcome. Future models of care need to incorporate early and increased access to non-exercise cardiac imaging techniques in order to meet the needs of this high-risk subgroup of patients.

Emergency percutaneous aortic balloon valvuloplasty in a nonagenarian

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Electrocardiogram changes causing a diagnostic dilemma

A 52-year-old, previously healthy man was brought to the emergency room following an episode of collapse. He denied chest pain, shortness of breath or palpitations. Apart from smoking, he did not have any other risk factors for venous thromboembolism or coronary artery disease. He had a heart rate of 96 beats/min, a blood pressure of 110/70 mmHg, a slightly elevated jugular venous pressure and an oxygen saturation of 98% on high-flow oxygen. Arterial blood gases showed a PO2 of 55.4 mmHg and a PCO2 of 33.5 mmHg. His 12-lead electrocardiogram (ECG) (Figure 1) showed diffuse ST segment depression in the anterior, inferior and lateral leads with ST elevation in lead aVR. Figure 1) A 12-lead electrocardiogram showing diffuse ST segment depression in the anterior, inferior and lateral leads with ST elevation in lead aVR In view of these ECG changes, an acute coronary event involving the left main stem or triple vessel coronary disease, and an acute pulmonary embolism were considered to be differential diagnoses. Bedside echocardiography revealed a grossly dilated and hypokinetic right ventricle, and the left ventricle was globally hypokinetic. The D-dimer level was elevated at 1261 ng/mL (reference range 0 ng/mL to 250 ng/mL) and the troponin T level was 0.27 ng/L (reference range 0 ng/mL to 0.1 ng/mL). A computed tomography pulmonary angiogram showed a large saddle thrombus in the right main pulmonary artery. There was also evidence of thrombus in the left upper and lower lobe branches. In view of the large embolus, right ventricular dilation and syncope, the patient received thrombolytic therapy. ST changes resolved (Figure 2), and right and left ventricular function improved remarkably over the next few days. Figure 2) A 12-lead electrocardiogram performed after thrombolytic therapy, showing resolution of ST changes The above ECG changes and echocardiographic features are indicative of severe right ventricular strain and myocardial ischemia due to acute massive pulmonary embolism.