Kuljit Singh

Systematic review and meta-analysis of incidence and correlates of recurrence of takotsubo cardiomyopathy

AIM Takotsubo cardiomyopathy (TTC) is a disorder of myocardial inflammation induced by high catecholamine levels and is associated with acute complications. In the long-term TTC is associated with a risk of single or multiple recurrences, but risk of such occurrences is not clear. We performed a systematic review and meta-analysis to identify and consolidate the evidence on the incidence and clinical correlates of cases of TTC recurrence. METHODS A comprehensive search of four major databases (EMBASE, OVID Medline, PubMed and Google Scholar) was performed from their inception to first week of Jan 2014. We included original research studies, recruiting ≥ 5 participants, with ≥ 3 months follow-up, published in English language that reported data on recurrence in patients with TTC. RESULTS Out of 298 studies searched, 31 cohorts (1664 TTC patients) were included in the analyses. Out of 74 cases of recurrence, with a mean follow-up of 24.5 months (95% CI, 19.3 to 33 months), extensive recurrence data were available for 23 cases. Cumulative incidence of recurrence was approximately 5% at 6 years. Annual rate of recurrence was approximately 1.5%. Furthermore, 14% of cases had recurrent chest pain and 11% reported dyspnea without definite evidence of recurrent TTC. Discharge medications at index admission included β-adrenoceptor antagonists (BB) in 66.8% and ACE inhibitors (ACEi) and ARB in 67.4%. Recurrence rate was independent of clinic utilization of BB prescription, but inversely correlated (r=-0.45, p=0.016) with ACEi/ARB prescription. Patients with severe TTC at index admission were noted to have more recurrences. CONCLUSIONS (1) TTC is associated with only 1-2% annual recurrence rate but substantially greater frequency of ongoing symptoms. (2) ACEi/ARB rather than BB may reduce risk of recurrence.

Statins use and risk of depression: A systematic review and meta-analysis

IMPORTANCE Statin use has been associated with depression; however studies of the association between statin use and depression have yielded mixed results. OBJECTIVE To determine whether statin use is associated with depression and to evaluate the evidence supporting this association. DATA SOURCES Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched through December 28, 2012. STUDY SELECTION We included studies that evaluated exposure to statins, reported the development of depression, and relative risks or odds ratios (ORs) or provided data for their estimation. Two reviewers screened 981 abstracts independently using a standardized form, reviewed full text of 59 selected articles, and included 7 studies in this metaanalysis. DATA EXTRACTION AND SYNTHESIS Study design, statin exposure, development of depression, and study quality were extracted by 2 independent reviewers. A pooled OR with 95% confidence interval (CI) was estimated using the random-effects model and heterogeneity was assessed using Cochrans Q test and the I(2) statistic. RESULTS Seven observational studies (4 cohort, 2 nested case-control, and 1 cross-sectional) from 5 countries enrolling 9187 patients were included. Statin users were 32% less likely to develop depression than nonusers (adjusted OR, 0.68; 95% CI, 0.52-0.89). Modest heterogeneity was observed between the studies (I(2)=55%, P=0.01), which could be accounted for by one study, exclusion of which removed the heterogeneity (P=0.40, I(2)=2%) and further strengthened the antidepressant effect of statin (adjusted OR, 0.63; 95% CI, 0.43-0.93). Heterogeneity could not be explained by study design or study population. The quality of supporting evidence was fair. CONCLUSIONS AND RELEVANCE This systematic review and meta-analysis suggests that statin use is associated with lower risk for depression. However, higher-quality studies are needed to confirm the magnitude of this association.

Dissociation between severity of takotsubo cardiomyopathy and presentation with shock or hypotension.

Takotsubo cardiomyopathy (TTC) is increasingly well‐recognized as a cause of chest‐pain syndromes, especially in aging females. The most common complications of TTC occur in the first 24 hours post onset of symptoms and include shock and/or arrhythmias.

Efficacy of Radial Versus Femoral Access in the Acute Coronary Syndrome: Is it the Operator or the Operation That Matters?

In the recently published MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) trial, the use of transradial access (TRA) compared to transfemoral access (TFA) during percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) was associated with a reduction in net adverse cardiovascular events. However, the results of MATRIX must be interpreted with caution due to several limitations including the strong modulating effect of operator/center experience on the relative efficacy of TRA and the inclusion of 2 distinct patient populations (ST-segment elevation and non-ST-segment elevation ACS). Therefore, although important, the results of MATRIX have strong limitations and are not sufficient to definitively identify an approach of choice during PCI for ACS. Further research is needed before strong, evidence-based recommendations regarding the approach of choice during PCI for ACS can be made.

A meta analysis of current status of alcohol septal ablation and surgical myectomy for obstructive hypertrophic cardiomyopathy

Our objective was to perform an updated systematic review to compare the efficacy and short‐ and long‐term mortality of surgical myectomy (SM) and alcohol septal ablation (ASA) by including most recent and largest cohort studies published in last few years. Background: SM and ASA are the two invasive strategies used to relieve left ventricular outflow tract obstruction (LVOTO) in patients with drug refractory symptomatic hypertrophic cardiomyopathy (HCM). In the absence of a randomized trial, we tried to compare the pros and cons of the two procedures using a systematic review and meta‐analysis. Method: A comprehensive search of three major databases was performed. We included original research studies comparing data on ASA and SM. Of 1,143 citations, 10 studies were included in the analysis. Results: A total of 805 patients underwent ASA and 1,019 underwent SM. Patients undergoing SM were younger (MD 6.3, P = 0.0001) and had higher reduction in the LVOT gradient (MD −9.56, P = 0.05). However, there was similar resolution of class III and IV symptoms between the two groups (P = 0.56). There was no difference in sudden cardiac death (SCD) (P = 0.93), short‐term (P = 0.36), long‐term all cause (P = 0.27), and long‐term cardiac mortality (P = 0.58). Patients undergoing ASA had higher incidence of post procedure device implantation (OR 3.09, P < 0.00001). Conclusion: No significant difference in symptom relief was noted between the two approaches. ASA was as safe a myectomy with regards to SCD, short‐term, and long‐term mortality.

Natural History of Cardiac Arrest in Patients With Takotsubo Cardiomyopathy

Cardiac arrest (CA) is relatively rare but lethal complication of takotsubo cardiomyopathy (TTC). In most instances, patients are diagnosed with TTC after CA, making it difficult to distinguish if TTC is the precipitant or the consequence of the index event. In this systematic review, patient-level data were obtained to seek out the characteristics of patients in whom the underlying cause of CA is TTC. A comprehensive search of 4 major databases (Embase, Ovid MEDLINE, PubMed, and Google Scholar) was performed from their inception to the last week of September 2014. Of 186 citations, 62 case studies were included in the analysis, providing patient-level data on 77 patients. In 60 patients (78%), the diagnosis of TTC was made after CA. Patients presenting with CA were younger (mean age 49.5 ± 16 vs 64.9 ± 11 years, p <0.0001) and had relatively shorter corrected QT interval (mean 530 ± 101 vs 616 ± 140 ms) on electrocardiography. TTC-related hypotension was the major cause of CA in the acute phase, while a long corrected QT interval triggered CA in the subacute (24- to 72-hour) phase. In 11 patients, CA was not directly instigated by TTC despite a left ventricular appearance matching TTC. In conclusion, in TTC, CA typically develops within the first 3 days of presentation and is the result of long corrected QT interval-induced polymorphic ventricular tachycardia. Secondary TTC, in which patients present with typical left ventricular features after CA, likely represents a distinct cohort in which identifiable inheritable arrhythmias or structural heart disease should be sought.

Dissociation of Early Shock in Takotsubo Cardiomyopathy from either Right or Left Ventricular Systolic Dysfunction

BACKGROUND Takotsubo cardiomyopathy (TTC) is often associated with hypotension and shock. However, development of hypotension/shock in TTC is not closely related to extent of left ventricular (LV) hypokinesis. We sought to determine whether additional right ventricular (RV) involvement in TTC might contribute to hypotension and shock development and thus to prolonged hospital stay (PHS). METHODS We evaluated 102 consecutive TTC patients with acute transthoracic echocardiography (TTE) to detect RV hypokinesis. Correlates of hypotension, shock and PHS were identified by univariate and multivariate analyses. RESULTS Of the 102 patients evaluated, 33% had RV hypokinesis but only 9% had extensive RV involvement. Within the first 24 hours of admission, severe hypotension (systolic blood pressure (SBP) ≤ 90 mmHg) occurred in 21% of the patients and shock (hypotension + peripheral organ hypo-perfusion) in 16.6% of cases. RV involvement was a univariate but not a multivariate correlate of either hypotension or shock and did not result in PHS. On the other hand, RV involvement predicted more extensive LV hypokinesis and LV systolic dysfunction. CONCLUSIONS In TTC, RV hypokinesis occurs in approximately 33% of cases and correlates with more severe LV wall motion abnormality but not with development of hypotension or shock. These data therefore reinforce previous findings that hypotension/shock in TTC are not purely by impaired cardiac output.

Ticagrelor in Triple Antithrombotic Therapy: Predictors of Ischemic and Bleeding Complications

Patients on dual antiplatelet therapy following percutaneous coronary intervention often have indications for concurrent oral anticoagulation or triple antithrombotic therapy (TT). Although TT may decrease ischemic complications, it may confer increased bleeding risk.

Relation of Delayed Recovery of Myocardial Function After Takotsubo Cardiomyopathy to Subsequent Quality of Life

Takotsubo cardiomyopathy (TTC) has generally been regarded as a relatively transient disorder, characterized by reversible regional left ventricular systolic dysfunction. However, most patients with TTC experience prolonged lassitude or dyspnea after acute attacks. Although this might reflect continued emotional stress, myocardial inflammation and accentuated brain-type natriuretic peptide (BNP) release persist for at least 3 months. We therefore tested the hypotheses that this continued inflammation is associated with (1) persistent contractile dysfunction and (2) consequent impairment of quality of life. Echocardiographic parameters (global longitudinal strain [GLS], longitudinal strain rate [LSR], and peak apical twist [AT]) were compared acutely and after 3 months in 36 female patients with TTC and 19 age-matched female controls. Furthermore, correlations were sought between putative functional anomalies, inflammatory markers (T2 score on cardiovascular magnetic resonance, plasma NT-proBNP, and high-sensitivity C-reactive protein levels), and the physical composite component of SF36 score (SF36-PCS). In TTC cases, left ventricular ejection fraction returned to normal within 3 months. GLS, LSR, and AT improved significantly over 3-month recovery, but GLS remained reduced compared to controls even at follow-up (-17.9 ± 3.1% vs -20.0 ± 1.8%, p = 0.003). Impaired GLS at 3 months was associated with both persistent NT-proBNP elevation (p = 0.03) and reduced SF36-PCS at ≥3 months (p = 0.04). In conclusion, despite normalization of left ventricular ejection fraction, GLS remains impaired for at least 3 months, possibly as a result of residual myocardial inflammation. Furthermore, perception of impaired physical exercise capacity ≥3 months after TTC may be explained by persistent myocardial dysfunction.

β2 Agonist for the Treatment of Acute Lung Injury: A Systematic Review and Meta-analysis

BACKGROUND: The use of β2 agonist as an intervention for acute lung injury (ALI) and ARDS patients is controversial, so we performed a systematic review and meta-analysis of the published randomized controlled trials of using β2 agonists to improve outcomes (mortality and ventilator free days) among patients with ALI/ARDS. METHODS: A comprehensive search of 7 major databases (Ovid MEDLINE In-Process and other non-indexed citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials (CENTRAL), Ovid Cochrane Database of Systematic Reviews, Web of Science, and Scopus) for randomized controlled trials using β2 agonists for ALI from their origin to March 2013 was conducted. The effect size was measured by relative risk for dichotomous outcomes, and mean difference for continuous outcomes, with 95% CI. The statistical heterogeneity between the studies was assessed with the Cochran Q test and I2 statistic. The heterogeneity of > 50% was considered significant for the analysis. The Cochrane risk of bias tool was used to ascertain the quality of the included studies. RESULTS: Out of 219 studies screened, 3 randomized controlled trials reported mortality and ventilator-free days, in 646 ALI/ARDS subjects. Of the 646 subjects, 334 (51.7%) received β2 agonist and 312 (48.3%) received placebo. There was no significant decrease in 28-day mortality or hospital mortality in the β2-agonist group: relative risk 1.04, 95% CI 0.50–2.16, and relative risk 1.22, 95% CI 0.95–1.56, respectively. The ventilator-free days and organ-failure-free days were significantly lower for the ALI subjects who received β2 agonists: mean difference −2.19 days (95% CI −3.68 to −1.99 d) and mean difference −2.04 days (95% CI −3.74 to −0.35 d), respectively. CONCLUSIONS: In subjects with ALI/ARDS, β2 agonists were not only nonbeneficial in improving the survival, but were harmful and increased morbidity (reduced organ-failure-free days and ventilator-free days). The current evidence discourages the use of β2 agonist in ALI/ARDS patients. (International Prospective Register of Systematic Reviews, http://www.crd.york.ac.uk/prospero, 2012:CRD42012002616.)