Search

Background: No studies assessed impact of atrial flutter (AFL) ablation on outcomes in patients with AFL and concurrent heart failure (HF). Objectives: To assess the effect of AFL ablation on mortality and HF readmissions in patients with AFL and HF. Methods: This retrospective cohort study identified 15,952 patients with AFL and HF from the 2016–17 Nationwide Readmissions Database. The primary outcome was a composite of all-cause mortality and/or HF readmission at 1 year. Secondary outcomes included HF readmission, all-cause mortality, and atrial fibrillation (AF) readmission at 1 year. Propensity score match (1:2) algorithm was used to adjust for confounders. Cox proportional hazard regression was used to generate hazard ratios. Results: Of the 15,952 patients, 9889 had heart failure with reduced ejection fraction (HFrEF) and 6063 had heart failure with preserved ejection fraction (HFpEF). In the matched HFrEF cohort (n = 5421), the primary outcome was significantly lower in patients undergoing ablation (HR 0.72, 95% CI 0.61–0.85, P < .001). HF readmission (HR 0.73, 95% CI 0.61–0.89, P = .001), all-cause mortality (HR 0.62, 95% CI 0.46–0.85, P = .003), and AF readmission (HR 0.63, 95% CI 0.48–0.82, P = .001) were also significantly reduced. In the matched HFpEF cohort (n = 2439), the primary outcome was lower in the group receiving ablation but was not statistically significant (HR 0.80, 95% CI 0.63–1.01, P = .065). Conclusion: In patients with AFL and HFrEF, AFL ablation was associated with lower mortality and HF readmissions at 1 year. Patients with AFL and HFpEF did not show a similar significant reduction in the primary outcome.

ObjectivesTo examine the relationship between pericardial fat (PCF) and cardiac structure and function among HIV-infected patients in the sub-Saharan African country of Uganda. People living with HIV (PLHIV) have altered fat distribution and an elevated risk for heart failure. Whether altered quantity and radiodensity of fat surrounding the heart relates to cardiac dysfunction in this population is unknown.MethodsOne hundred HIV-positive Ugandans on antiretroviral therapy were compared with 100 age and sex-matched HIV-negative Ugandans; all were >45 years old with >1 cardiovascular disease risk factor. Subjects underwent ECG-gated non-contrast cardiac CT and transthoracic echocardiography with speckle tracking strain imaging. Multivariable linear and logistic regression models were used to explore the association of PCF with echocardiographic outcomes.ResultsMedian age was 55% and 62% were female. Compared with uninfected controls, PLHIV had lower body mass index (27 vs 30, p=0.02) and less diabetes (26% vs 45%, p=0.005). Median left ventricular (LV) ejection fraction was 67%. In models adjusted for traditional risk factors, HIV was associated with 10.3 g/m2 higher LV mass index (LVMI) (95% CI 3.22 to 17.4; p=0.005), 0.87% worse LV global longitudinal strain (GLS) (95% CI −1.66 to −0.07; p=0.03) and higher odds of diastolic dysfunction (OR 1.96; 95% CI 0.95 to 4.06; p=0.07). In adjusted models, PCF volume was significantly associated with increased LVMI and worse LV GLS, while PCF radiodensity was associated with worse LV GLS (all pConclusionsIn Uganda, HIV infection, PCF volume and density are associated with abnormal cardiac structure and function.

Accurate identification of left ventricular masses (LVM) can be challenging, and if incorrect, may have devastating consequences. While transthoracic echocardiography is often the first test to identify intracardiac masses, cardiac MRI (CMRI) allows for better anatomical definition and tissue characterisation. We present a case of a 51-year-old man who presented with 4 weeks of shortness of breath, found on echocardiogram to have severely reduced LV function and a 2.5×4.0 cm LVM with a hypolucent/cystic core. Due to the unusual appearance, CMRI was required for confirmation of an LV thrombus. This case highlights the importance of multimodality imaging in the discovery and identification of LVM.

Background Pulmonary arterial hypertension (PAH) is a potentially serious cause of dyspnea and exercise limitation in patients with HIV infection. In this trial, we propose using exercise MRI in conjunction with cardiopulmonary testing to delineate PAH from other causes of cardiovascular dysfunction, identify individuals with exercise-induced PAH who are at high risk of developing resting PAH, and provide longitudinal estimates of progression of PAH and right ventricular function. Methods In this prospective observational study, HIV patients with dyspnea and exercise limitation in the absence of identifiable causes and those who meet the inclusion criteria will be enrolled based on resting pulmonary artery pressure (≤ or >40 mmHg) on a screening echocardiogram and exercise limitation on the Modified Medical Research Council dyspnea scale. Patients without evidence of resting PAH will be enrolled into both rest and exercise MRI and cardiopulmonary testing protocol, whereas patients with evidence of PAH on resting echocardiograms will undergo only resting cardiac MRI studies to evaluate right ventricular function and fibrosis. Both patient subgroups will be followed for 24 months to obtain longitudinal progression of the disease. In a sub-study, we will further analyze inflammatory variables that may predict these changes, thus allowing early identification of these patients. Implications and conclusions This trial will be the first study to provide an understanding of the mechanisms underpinning the functional deterioration of the right ventricle in patients with HIV and will impart insight into the immune mediators of PAH progression and right ventricular functional deterioration in patients with HIV-PAH.

Background The efficacy and safety of colchicine for the primary prevention of the postpericardiotomy syndrome (PPS), postoperative effusions, and postoperative atrial fibrillation (POAF) remain uncertain. Although preliminary data from a single trial of colchicine given for 1 month postoperatively (COPPS trial) were promising, the results have not been confirmed in a large, multicenter trial. Moreover, in the COPPS trial, colchicine was given 3 days postoperatively. Methods The COPPS-2 study is a multicenter, double-blind, placebo-controlled randomized trial. Forty-eight to 72 hours before planned cardiac surgery, 360 patients, 180 in each treatment arm, will be randomized to receive placebo or colchicine without a loading dose (0.5 mg twice a day for 1 month in patients weighing GT = 70 kg and 0.5 mg once for patients weighing LT 70 kg or intolerant to the highest dose). The primary efficacy end point is the incidence of PPS, postoperative effusions, and POAF at 3 months after surgery. Secondary end points are the incidence of cardiac tamponade or need for pericardiocentesis or thoracentesis, PPS recurrence, disease-related admissions, stroke, and overall mortality. Conclusions The COPPS-2 trial will evaluate the use of colchicine for the primary prevention of PPS, postoperative effusions, and POAF, potentially providing stronger evidence to support the use of preoperative colchicine without a loading dose to prevent several postoperative complications. ClinicalTrials. gov Identifier

Investigating the pathophysiological importance of the molecular and mechanical development of cardiomyopathy is critical to find new and broader means of protection against this disease that is increasing in prevalence and impact. The current available treatment options for cardiomyopathy mainly focus on treating symptoms and strive to make the patient more comfortable while preventing progression of disease and sudden death. The proto-oncogene c-Myc (Myc) has been shown to be increased in many different types of heart disease, including hypertrophic cardiomyopathy, before any signs of the disease are present. As the mechanisms of action and multiple pathways of dependent actions of Myc are being dissected by many research groups, inhibition of Myc is becoming an attractive paradigm for prevention and treatment of cardiomyopathy and heart failure. Elucidating the role Myc plays in the development, propagation and perpetuation of cardiomyopathy and heart failure will one day translate into potential therapeutics for cardiomyopathy.

To investigate the local effects of angiotensin II on the heart, we created a mouse model with 100-fold normal cardiac angiotensin-converting enzyme (ACE), but no ACE expression in kidney or vascular endothelium. This was achieved by placing the endogenous ACE gene under the control of the alpha-myosin heavy chain promoter using targeted homologous recombination. These mice, called ACE 8/8, have cardiac angiotensin II levels that are 4.3-fold those of wild-type mice. Despite near normal blood pressure and a normal renal function, ACE 8/8 mice have a high incidence of sudden death. Both histological analysis and in vivo catheterization of the heart showed normal ventricular size and function. In contrast, both the left and right atria were three times normal size. ECG analysis showed atrial fibrillation and cardiac block. In conclusion, increased local production of angiotensin II in the heart is not sufficient to induce ventricular hypertrophy or fibrosis. Instead, it leads to atrial morphological changes, cardiac arrhythmia, and sudden death.

Increases in type 1 phosphatase (PP1) activity have been observed in end stage human heart failure, but the role of this enzyme in cardiac function is unknown. To elucidate the functional significance of increased PP1 activity, we generated models with (i) overexpression of the catalytic subunit of PP1 in murine hearts and (ii) ablation of the PP1-specific inhibitor. Overexpression of PP1 (threefold) was associated with depressed cardiac function, dilated cardiomyopathy, and premature mortality, consistent with heart failure. Ablation of the inhibitor was associated with moderate increases in PP1 activity (23%) and impaired beta-adrenergic contractile responses. Extension of these findings to human heart failure indicated that the increased PP1 activity may be partially due to dephosphorylation or inactivation of its inhibitor. Indeed, expression of a constitutively active inhibitor was associated with rescue of beta-adrenergic responsiveness in failing human myocytes. Thus, PP1 is an important regulator of cardiac function, and inhibition of its activity may represent a novel therapeutic target in heart failure.

Phospholamban is the regulator of the cardiac sarcoplasmic reticulum (SR) Ca(2+)-ATPase activity and an important modulator of basal contractility in the heart. To determine whether all the SR Ca(2+)-ATPase enzymes are subject to regulation by phospholamban in vivo, transgenic mice were generated which overexpressed phospholamban in the heart, driven by the cardiac-specific alpha-myosin heavy chain promoter. Quantitative immunoblotting revealed a twofold increase in the phospholamban protein levels in transgenic hearts compared to wild type littermate hearts. The transgenic mice showed no phenotypic alterations and no changes in heart/body weight, heart/lung weight, and cardiomyocyte size. Isolated unloaded cardiac myocytes from transgenic mice exhibited diminished shortening fraction (63%) and decreased rates of shortening (64%) and relengthening (55%) compared to wild type (100%) cardiomyocytes. The decreases in contractile parameters of transgenic cardiomyocytes reflected decreases in the amplitude (83%) of the Ca2+ signal and prolongation (131%) in the time for decay of the Ca2+ signal, which was associated with a decrease in the apparent affinity of the SR Ca(2+)-ATPase for Ca2+ (56%), compared to wild type (100%) cardiomyocytes. In vivo analysis of left ventricular systolic function using M mode and pulsed-wave Doppler echocardiography revealed decreases in fractional shortening (79%) and the normalized mean velocity of circumferential shortening (67%) in transgenic mice compared to wild type (100%) mice. The differences in contractile parameters and Ca2+ kinetics in transgenic cardiomyocytes and the depressed left ventricular systolic function in transgenic mice were abolished upon isoproterenol stimulation. These findings indicate that a fraction of the Ca(2+)-ATPases in native SR is not under regulation by phospholamban. Expression of additional phospholamban molecules results in: (a) inhibition of SR Ca2+ transport; (b) decreases in systolic Ca2+ levels and contractile parameters in ventricular myocytes; and (c) depression of basal left ventricular systolic function in vivo.

Echocardiographic and hemodynamic data were measured in nine closed chest dogs during graded cardiac tamponade (pericardial pressure 5, 10, 15 mm Hg) before and after production of diffuse acute ischemic right ventricular dysfunction. Right ventricular dysfunction was produced by intracoronary injection of nonradioactive microspheres (mean diameter +/- SD 54 +/- 4 microns) and caused a significant increase in right atrial pressure (7.6 +/- 1.4 vs. 1.6 +/- 1 mm Hg, p less than 0.001) and cross-sectional areas of both the right atrium (8.3 +/- 0.3 vs. 5.6 +/- 0.2 cm2, p less than 0.001) and right ventricle (8.8 +/- 0.4 vs. 5.7 +/- 0.4 cm2, p less than 0.001). Right atrial and ventricular collapse required a significantly larger pericardial effusion and pericardial pressure after right ventricular infarction than before. Mean aortic pressure had fallen 1.9 +/- 2% and 6.5 +/- 6.9% at the time of right atrial collapse (p = NS before vs. after right ventricular dysfunction) and 3 +/- 4.1% and 20.1 +/- 20.8% at the time of right ventricular collapse (p less than 0.03) before and after right ventricular dysfunction, respectively. In the presence of ischemic right ventricular dysfunction, echocardiographic signs of cardiac tamponade are less sensitive and occur later in the hemodynamic progression of cardiac tamponade. Pulsus paradoxus with cardiac tamponade was not prevented by coexisting ischemic right ventricular dysfunction.

Atrial fibrillation (AF) is a common arrhythmia, affecting approximately 5% of the population older than 65 years; the arrhythmia is associated with significant morbidity and mortality, and it is challenging and often frustrating to treat [(1,2)][1]. There is a tendency for AF to become chronic and