Ischemic cardiomyopathy: epidemiology, pathophysiology, outcomes, and therapeutic options.

Ischemic cardiomyopathy (ICM) is the most prevalent cause of heart failure (HF) in developed countries, with significant morbidity and mortality, despite constant improvements in the management of coronary artery disease. Current literature on this topic remains fragmented. Therefore, this review aimed to summarize the most recent data on ICM, focusing on its definition, epidemiology, outcomes, and therapeutic options. The most widely accepted definition is represented by a left ventricular dysfunction in the presence of significant coronary artery disease. The prevalence of ICM is largely influenced by age and sex, with older individuals and males being more affected. Its pathophysiology is characterized by plaque buildup, thrombus formation, hypoperfusion, ischemic cell death, and left ventricular remodeling. Despite improvements in therapy, ICM still represents a public health burden, with a 1-year mortality rate of 16% and a 5-year mortality rate of approximately 40% in the USA and Europe. Therefore, optimization of cardiovascular function, prevention of progressive remodeling, reduction of HF symptoms, and improved survival are the main goals of treatment. Therapeutic options for ICM include lifestyle changes, optimal medical therapy, revascularization, device therapy, mechanical circulatory support, and cardiac transplantation. Personalized management strategies and tailored patient care are needed to improve the outcomes of patients with ICM.

Point of Care Ultrasound (POCUS) in the Management of Heart Failure: A Narrative Review.

Assessing for volume overload is a key component of both short and long-term management of heart failure patients. Physical examination findings are neither sensitive nor specific for detecting congestion, and subclinical congestion may not be evident at the time of examination. Point of care ultrasound (POCUS) is an efficient and non-invasive way to assess heart failure patients for volume overload. The aim of our narrative review is to summarize how each of the following ultrasound modalities can be used to assess for congestion in the heart failure population: 2D and Doppler echocardiography, lung ultrasound, inferior vena cava ultrasound, internal jugular vein ultrasound, and venous excess grading. While each of these modalities has their limitations, their use in the acute and outpatient space offers the potential to reduce heart failure readmissions and mortality.

Sacubitril/Valsartan and Cognitive Outcomes in Heart Failure With Reduced Ejection Fraction.

Background: Recent trial data refute concerns about neurocognitive off-target effects of neprilysin inhibition with sacubitril and suggest benefit in patients with heart failure and ejection fraction >40%. We hypothesized that sacubitril/valsartan is associated with improved cognitive outcomes in patients with heart failure and reduced ejection fraction (HFrEF). Objectives: The purpose of this study was to compare 3-year cognitive outcomes in patients with HFrEF who receive sacubitril/valsartan vs angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). Methods: Retrospective cohort study of: 1) 11,313 adults with HFrEF (International Classification of Diseases-10th Revision-Clinical Modification [ICD-10-CM] codes: I50.2 or I50.4) started on sacubitril/valsartan between 1/1/2015 and 12/31/2019; and 2) 11,313 propensity matched patients receiving ACEI/ARB during that time. Data were obtained from the TriNetX Research Network, encompassing 41 health care organizations in the United States. Primary endpoint was the composite of cognitive decline (ICD-10-CM: R41.8), dementia (ICD-10-CM: F01-F03), and Alzheimer's disease (ICD-10-CM: G30). Results: At 3 years, 858 patients on sacubitril/valsartan met the primary endpoint vs 1,209 on ACEI/ARB (3-year incidence: 10.7% vs 15.0%; HR: 0.69; 95% CI: 0.63-0.75; P < 0.001), with consistently lower rates of cognitive decline (9.5% vs 13.3%; HR: 0.69; 95% CI: 0.63-0.76; P < 0.001), dementia (3.4% vs 5.0%; HR: 0.65; 95% CI: 0.57-0.77; P < 0.001), and Alzheimer's disease (0.6% vs 1.3%; HR: 0.48; 95% CI: 0.35-0.66; P < 0.001) in the sacubitril/valsartan cohort. Results were consistent in matched sex and race subgroups. Three-year mortality was 22.0% on sacubitril/valsartan vs 24.6% on ACEI/ARB (HR: 0.89; 95% CI: 0.84-0.94; P < 0.001). Conclusions: Sacubitril/valsartan was associated with lower 3-year rates of neurocognitive disorders when compared to ACEI/ARBs in patients with HFrEF.

Safety of Outpatient Milrinone Infusion in End-Stage Heart Failure: ICD-Level Data on Atrial Fibrillation and Ventricular Tachyarrhythmias.

BACKGROUND: Milrinone infusion is one of a few select "non-device" therapies for patients with New York Heart Association (NYHA) class IV, stage D heart failure, which has been associated with an increase in ventricular tachyarrhythmia and atrial fibrillation. Milrinone improves hemodynamics and provides symptomatic relief. Many patients with end-stage heart failure die from cardiac pump failure, and the impact of ventricular tachyarrhythmia and atrial fibrillation on their mortality is unclear. METHODS: This is a retrospective study of 98 consecutive patients receiving outpatient milrinone in a single center from 2008 to 2016. The primary endpoint of the study was overall survival on milrinone. Secondary endpoints were incidence of post-milrinone implantable cardioverter defibrillator (ICD) shocks and development of ventricular tachyarrhythmia or atrial fibrillation. RESULTS: Median survival was 581 ± 96 days with no difference between those with prior ventricular tachyarrhythmia and those without at 1 month (92% vs 97%, P = 0.34), 6 months (67% vs 73%, P = 0.75), and 12 months (67% vs 61%, P = 0.88). Seven out of 12 (58%) patients with prior ventricular tachyarrhythmia had ICD shocks, as compared to 5 out of 78 (6.4%) (P <0.001). Thirty-five patients had atrial fibrillation prior to starting milrinone, which decreased to 72% (P <0.05) by the third follow-up time period (7-9 months). Amiodarone use was protective against new onset atrial fibrillation. CONCLUSIONS: Patients with stage D heart failure with a history of ventricular tachyarrhythmia have similar survival on outpatient milrinone compared to those without. However, those with prior ventricular tachyarrhythmia received more ICD shocks for more ventricular tachyarrhythmias. Milrinone remains a viable therapy for patients with stage D heart failure with limited therapeutic options.

Ranolazine: A New Anti-Ischemic Drug Which Affects Myocardial Energetics.

Ranolazine is a new, orally active pharmacologic agent that experimentally has been shown to favorably affect myocardial metabolism during myocardial ischemia. It has no direct action on myocardial hemodynamics but appers to improve ventricular functioning by blocking uptake of free fatty acids by the heart while shifting metabolism to anaerobic glycolysis during myocardial ischemia. Preliminary clinical studies suggest a dose-dependent antianginal, and anti-ischemic effect and an excellent safety profile for this unique drug. However, the results of a recent double-blind efficacy and safety study showed no antianginal effect of ranolazine (30--120 mg thrice daily) when compared to placebo.

A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation: the tacrolimus in combination, tacrolimus alone compared (TICTAC) trial.

BACKGROUND: Cardiac transplantation, a procedure nearly abandoned in the 1970s, has evolved into the standard of care for appropriate patients with end-stage heart failure. Much of this success has been due to improvements in immunosuppression, including the introduction of a triple-drug regimen. Retrospective reports suggested that single-drug immunosuppression with tacrolimus was feasible. As such, a prospective, randomized trial was conducted to test this approach. METHODS AND RESULTS: One hundred fifty adult de novo heart transplant recipients were enrolled in a prospective, randomized, controlled, open-label trial comparing tacrolimus monotherapy (MONO) with tacrolimus and mycophenolate mofetil therapy (COMBO). Corticosteroids were used in the early postoperative period but discontinued in all patients over 8 to 9 weeks. The primary end point was the composite biopsy score at 6 months after transplant. Patients were followed for 1 to 5 years. The composite biopsy score was similar between groups at 6 and 12 months: 6-month MONO, 0.70 ± 0.44 (95% confidence interval, 0.60 to 0.80) versus COMBO, 0.65 ± 0.40 (95% confidence interval, 0.55 to 0.74; P=0.44). Allograft vasculopathy was assessed by angiography and intravascular ultrasound, with no significant differences noted. Three-year survival was also similar (92.4% MONO versus 97% COMBO; P=0.58, log-rank). CONCLUSIONS: Addition of mycophenolate to single-agent immunosuppression did not provide an advantage over single-agent immunosuppression in terms of rejection, allograft vasculopathy, or 3-year survival. Corticosteroids, which have traditionally been a mainstay of therapy, were successfully discontinued in all patients. These conclusions are tempered by the limited statistical power associated with a sample size of only 150 patients. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00299221.