Spironolactone Reduces Aortic Stiffness in Patients With Resistant Hypertension Independent of Blood Pressure Change.

Background Aortic stiffness is an independent predictor of cardiovascular events in patients with arterial hypertension. Resistant hypertension is often linked to hyperaldosteronism and associated with adverse outcomes. Spironolactone, a mineralocorticoid receptor antagonist, has been shown to reduce both the arterial blood pressure (BP) and aortic stiffness in resistant hypertension. However, the mechanism of aortic stiffness reduction by spironolactone is not well understood. We hypothesized that spironolactone reduces aortic stiffness in resistant hypertension independently of BP change. Methods and Results Patients with uncontrolled BP (≥140/90 mm Hg) despite use of ≥3 antihypertensive medications (including diuretics) were prospectively recruited. Participants were started on spironolactone at 25 mg/d, and increased to 50 mg/d at 4 weeks while other antihypertensive medications were withdrawn to maintain constant mean BP. Phase-contrast cardiac magnetic resonance imaging of the ascending aorta was performed in 30 participants at baseline and after 6 months of spironolactone treatment to measure aortic pulsatility, distensibility, and pulse wave velocity. Pulse wave velocity decreased (6.3±2.3 m/s to 4.5±1.8 m/s, P<0.001) and pulsatility and distensibility increased (15.9%±5.3% to 22.1%±7.9%, P<0.001; and 0.28%±0.10%/mm Hg to 0.40%±0.14%/mm Hg, P<0.001, respectively) following 6 months of spironolactone. Conclusions Our results suggest that spironolactone improves aortic properties in resistant hypertension independently of BP, which may support the hypothesis of an effect of aldosterone on the arterial wall. A larger prospective study is needed to confirm our findings.

Persistent mitral regurgitation after left ventricular assist device: a clinical conundrum.

AIMS: Persistent mitral valve regurgitation (MR) after continuous flow left ventricular assist device implantation (cfLVAD) is associated with pulmonary hypertension and right ventricular failure with variable effects on survival across published studies. The aim of this study is to determine the incidence and predictors of persistent MR at 6-month follow-up after cfLVAD implantation and its impact on survival, haemodynamics, right ventricular function, and morbidity. METHODS AND RESULTS: We performed a retrospective review of all adult cfLVAD recipients from January 2012 to June 2017 at a single tertiary university hospital with follow-up until April 2019. Primary outcome was to compare survival between patients with no-to-mild compared with persistent moderate-to-severe MR at 6 months. Secondary outcomes included right heart failure (RHF), length of stay, re-hospitalizations, and composite of death, transplant, and pump exchange during the length of follow-up. Final analytic sample was 111 patients. The incidence of persistent moderate or severe MR at 6 months was 26%. Significant predictors of persistent MR at 6 months were left atrium dimension and volume. The group with persistent moderate-to-severe MR at 6 months had higher incidence of RHF at 6 months (45% vs. 25%, P = 0.04). There was no difference in survival at 1 year between the groups (no-to-mild MR 85.5%, moderate-to-severe MR 87.9%, Wilcoxon P-value = 0.63). There was no difference in re-hospitalizations, length of stay, composite of death, transplant, or pump exchange during the length of follow-up between the comparison groups. CONCLUSIONS: Persistent moderate-to-severe MR after cfLVAD implantation is present in one fourth of patients and is associated with increased incidence of RHF, higher mean pulmonary pressure, and pulmonary capillary wedge pressure with no effect on 1 year survival. Increased left atrium size was associated with persistent moderate-to-severe MR at 6 months.

Management of reproductive health after cardiac transplantation.

Pregnancy after cardiac transplantation poses immense challenges. Maternal risks include hypertensive disorders of pregnancy, rejection, and failure of the cardiac allograft that may lead to death. Fetal risks include potential teratogenic effects of immunosuppression and prematurity. Because of the high-risk nature of pregnancy in a heart transplant patient, management of reproductive health after cardiac transplantation should include preconception counseling to all women in the reproductive age group before and after cardiac transplantation. Reliable contraception is vital as nearly half of the pregnancies in this population are unintended. Despite the associated risks, successful pregnancies after cardiac transplantation have been reported. A multidisciplinary approach proposed in this review is essential for successful outcomes. A checklist for providers to guide management is provided.

Management of reproductive health in patients with pulmonary hypertension.

Pulmonary hypertension is characterized by elevated pulmonary artery pressure caused by several clinical conditions that affect pulmonary vasculature. Morbidity and death in this condition are related to the development of right ventricular failure. Normal physiologic changes that occur in pregnancy to support the growing fetus can pose hemodynamic challenges to the pregnant patient with pulmonary hypertension that results in increased morbidity and mortality rates. Current guidelines recommend that patients with known pulmonary hypertension be counseled against pregnancy. This review aims to provide clinicians with guidelines for preconception counseling, medication management, and delivery planning.

Emerging role of cardiovascular magnetic resonance imaging in the management of pulmonary hypertension.

Pulmonary hypertension (PH) is a clinical condition characterised by elevation of pulmonary arterial pressure (PAP) above normal range due to various aetiologies. While cardiac right-heart catheterisation (RHC) remains the gold standard and mandatory for establishing the diagnosis of PH, noninvasive imaging of the heart plays a central role in the diagnosis and management of all forms of PH. Although Doppler echocardiography (ECHO) can measure a range of haemodynamic and anatomical variables, it has limited utility for visualisation of the pulmonary artery and, oftentimes, the right ventricle. Cardiovascular magnetic resonance (CMR) provides comprehensive information about the anatomical and functional aspects of the pulmonary artery and right ventricle that are of prognostic significance for assessment of long-term outcomes in disease progression. CMR is suited for serial follow-up of patients with PH due to its noninvasive nature, high sensitivity to changes in anatomical and functional parameters, and high reproducibility. In recent years, there has been growing interest in the use of CMR derived parameters as surrogate endpoints for early-phase PH clinical trials. This review will discuss the role of CMR in the diagnosis and management of PH, including current applications and future developments, in comparison to other existing major imaging modalities.

Cardiac Function and Sudden Cardiac Death in Heart Failure With Preserved Ejection Fraction (from the TOPCAT Trial).

Patients with heart failure with preserved ejection fraction (HFpEF) have a significantly elevated risk of sudden cardiac death (SCD). However, few imaging data have been correlated to this risk. We evaluated the value of multiple echocardiographic markers of left ventricular (LV) function to predict SCD in HFpEF patients. The Treatment of Heart Failure with Preserved Ejection Fraction with Aldosterone Trial (TOPCAT)-Americas cohort was used to evaluate the echocardiographic predictors of SCD and/or aborted cardiac arrest (SCD/ACA). A retrospective cohort design was used. Cox proportional hazards and Poisson regression models were used to determine the associations between the risk of SCD/ACA and echocardiographic parameters: diastolic dysfunction grade, left ventricle ejection fraction, and LV global longitudinal strain (GLS) during follow-up. Impaired left ventricle ejection fraction and GLS were associated with SCD/ACA in univariate models (p = 0.007 and 0.002, respectively), but not diastolic function grade. After multivariate adjustment, only GLS remained a significant predictor of the incidence rate of SCD/ACA (p = 0.006). There was a 58% increase in the hazard of incident SCD/ACA for every 1 unit increase in GLS (1.58, 95%CI: 1.12 to 2.22, p = 0.009). These findings remained robust in the competing risk analyses. In conclusion, amongst the multiple echocardiographic parameters of LV function, GLS may help prognosticate the risk of SCD/ACA in HFpEF patients.

Leucocyte count predicts cardiovascular risk in heart failure with preserved ejection fraction: insights from TOPCAT Americas.

AIMS: Prior evidence has implicated leucocyte expansion in several cardiovascular disorders, including heart failure (HF) with reduced ejection fraction (rEF). However, the prognostic importance of leucocyte count in HF with preserved EF (HFpEF) remains largely unexplored. METHODS AND RESULTS: The Americas cohort of the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT-Americas) was used to evaluate the association between total leucocyte count and clinical outcomes in HFpEF. The primary outcome was a composite of aborted cardiac arrest, cardiovascular mortality, or hospitalization for HF. Secondary outcomes were hospitalization for HF, aborted cardiac arrest, stroke, non-fatal myocardial infarction (MI), cardiovascular mortality, non-cardiovascular mortality, and all-cause mortality. Survival models were used to identify the risk of the primary and secondary outcomes in those with leucocyte count above the median (7100 cells/µL), as compared to those with leucocyte count below the median, during the follow-up period. A total of 1746 (out of 1767; 99%) patients from TOPCAT-Americas were available for the analyses with a median follow up of 2.4 (25th to 75th percentile 1.4-3.9) years. Patients with leucocyte count >7100 cells/µL were 36% more likely to experience the primary endpoint compared to those with ≤7100 cells/µL (hazard ratio: 1.36, 95% confidence interval: 1.14-1.61). This association remained significant after extensive adjustment for potential confounders (hazard ratio: 1.27, 95% confidence interval: 1.06-1.52). We also observed a greater incidence of HF hospitalization and non-fatal MI in patients with higher leucocyte count. These associations remained robust on sensitivity analyses, suggesting a low probability of confounding. Exploratory analyses suggested that both higher leucocyte count (integrating the combined influence of both myeloid and lymphoid immune cells) and augmented platelet count (as a surrogate for myeloid immune cell expansion) in the same model were associated with the primary outcome (both P < 0.05). CONCLUSIONS: Leucocyte count >7100 cells/µL was independently associated with adverse clinical outcomes in HFpEF patients from TOPCAT-Americas. These results were primarily driven by the HF hospitalization outcome but were also accompanied by an excess of non-fatal MI. Further research is needed to define the mechanisms underlying our findings and their prognostic implications.

A Case of Heart Failure in a Patient With Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) can present with multiple cardiovascular pathologies, including pulmonary hypertension, valvular disease, pericarditis, myocarditis, and premature atherosclerosis. SLE medications can also cause cardiovascular side effects. We present a patient who developed a severe cardiomyopathy secondary to the hydroxychloroquine prescribed to treat her SLE. (Level of Difficulty: Beginner.).

Role of left ventricle deformation analysis in stress echocardiography for significant coronary artery disease detection: A diagnostic study meta-analysis.

BACKGROUND: We compared the diagnostic accuracy of longitudinal strain (LS) imaging during stress echocardiography with visual assessment of wall motion (WM) for detecting significant coronary artery disease (CAD). METHODS: Our systematic search included studies reporting diagnostic measures for LS imaging and visual assessment of WM for detecting significant CAD during stress echocardiography. Summary diagnostic accuracy measures including area under the curve (AUC), sensitivity, specificity, diagnostic odds ratio (DOR), and likelihood ratios (LRs) were estimated. RESULTS: In thirteen studies with 978 patients, ten studies used invasive coronary angiography as the reference standard. Pooled AUC for diagnosing significant CAD was 0.92 (95% confidence interval [CI] 0.89-0.94) for LS imaging as compared to 0.83 (95% CI 0.80-0.86), P < 0.001 for visual assessment of WM. LS imaging had higher sensitivity (88% [95% CI 84-92] vs 74% [95% CI 68-80], P < 0.001) and comparable specificity to visual assessment of WM (80% [95% CI 72-87] vs 83% [95% CI 74-90], P = 0.592). The DOR for LS imaging and visual assessment of WM was 31 and 15, P = 0.254, respectively. The positive LR was 4.5 for both; negative LR was 0.14 and 0.31, P = 0.002 for LS imaging and visual assessment of WM, respectively. CONCLUSIONS: Longitudinal strain imaging during stress echocardiography has better diagnostic accuracy for detecting significant CAD as compared to visual assessment of WM. Studies using larger sample size and standardized techniques of strain measurement are required to further ascertain the added advantage of strain measurement over visual assessment alone.

Use of Computed Tomography in Preoperative Planning for Heartware Left Ventricular Assist Device Placement.

Optimal left ventricular assist device (LVAD) cannula position is important for adequate ventricular unloading and LVAD function. Poor inflow cannula position predisposes to pump thrombosis, inotrope dependence, and mortality. We describe a novel technique of preoperative left ventricular apex marking using CT guidance and demonstrate in three cases the use of this method to achieve optimal inflow cannula positioning for lateral thoracotomy Heartware LVAD implantation.

Propafenone associated severe central nervous system and cardiovascular toxicity due to mirtazapine: a case of severe drug interaction.

We describe a rare case of severe drug-drug interaction between propafenone and mirtazapine leading to propafenone toxicity. A 69-year-old Caucasian male taking propafenone for atrial fibrillation was prescribed mirtazapine for insomnia. Subsequent to the first dose of mirtazapine the patient experienced seizures, bradycardia and prolonged QRS as well as QTc intervals on EKG. The patient was admitted to the ICU and recovered after supportive management. Propafenone is an established class IC antiarrhythmic drug commonly used in the treatment of atrial fibrillation. It is metabolized through the CYP4502D6 pathway. Five to 10 percent of Caucasians are poor metabolizers. Mirtazapine is a commonly prescribed antidepressant drug, which is also metabolized through and may modulate the CYP4502D6 pathway leading to altered metabolism of propafenone and possible adverse effects. In this case, toxicity was reversed once the offending drugs were discontinued. An extensive review of the literature revealed this to be the first described case of drug interaction between propafenone and mirtazapine.