**Author details**

Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial was conducted to investigate the effect of the PDE-5 inhibitor, on exercise capacity in HFpEF [57]. At the end of 24 weeks, long-term PDE-5 inhibition in HFpEF had no effect on maximal or submaximal exercise capacity, clinical status, quality of life, left ventricular remodeling, diastolic function parameters, or pulmonary artery systolic

It is known that in both the failing heart and in case of ischemia, the late sodium current is increased, leading to an Na+ accumulation in cardiac myocytes [58]. The increased Na+ concentration reverses the mode direction of the Na+/Ca2+exchanger, contributing to a Ca2+ overload in the cell. Increased diastolic Ca2+ impairs relaxation leading to diastolic dysfunction. By inhibiting the late Na+ channel, ranolazine is theoretically expected to prevent (or reduce) sodium accumulation in the myocyte. This should improve calcium extrusion through the Na+/Ca2+ exchanger and thereby improve relaxation of the myocardium. The Ranolazine for the Treatment of Diastolic Heart Failure (RALI-DHF) study was designed to evaluate the effect of ranolazine versus placebo on hemodynamics, measures of diastolic dysfunction and biomarkers in 20 patients with HFpEF [59]. After 30 min of infusion, significant decreases from baseline were observed in LVEDP and PCWP in the ranolazine group, but not in the placebo group. However, ranolazine had no effect on invasively determined relaxation

In the recent PARADIGM-HF trial, the patients taking LCZ 696 showed steep reduction in the primary endpoint of CV death/heart failure hospitalization [60]. McMurray et al. noted that a subgroup of patients in the reduced EF spectrum's high end, i.e., LVEF approaching 40%, also benefits to the same extent as the overall study group [61]. Solomon et al. conducted prospective comparison of Angiotensin Receptor Neprilysin Inhibitor (ARNi) with Angiotensin Receptor Blocker (ARB) on Management of heart failure with preserved ejection fraction, PARAMOUNT trial, a double-blind randomized trial in 301 patients with heart failure with HFpEF, which compared LCZ696 with valsartan [62]. The primary endpoint, the decline in NT-proBNP, was significantly greater in the LCZ696 group than in the valsartan group. After 36 weeks, both left atrial volume and dimension, which reflect left ventricular filling pressure, also declined more with LCZ696 and there was greater improvement in the New York Heart

These encouraging results with LCZ696 have provided the rationale for a large outcomes trial in HFpEF. Prospective Comparison of ARNI with ARB Global Outcomes in Heart Failure with Preserved Ejection Fraction (PARAGON-HF) will use a similar overall study design to that of PARAMOUNT to determine whether LCZ696 can reduce cardiovascular death or total HF hospitalizations in patients with HFpEF. PARAGON-HF will enroll 4,300 patients with

Diagnosis of HFpEF should only be made after complete workup and if noninvasive diagnostic data comprising of LA dilation, diastolic dysfunction and high natriuretic peptide levels,

Association (NYHA) functional class with LCZ696 than with valsartan.

pressure.

52 Cardiomyopathies - Types and Treatments

parameters and the noninvasive E/E′ ratio.

HFpEF until the end of 2016.

**7. Future perspectives**

Hakan Altay\* and Seckin Pehlivanoglu

\*Address all correspondence to: sakaltay@yahoo.com

Cardiology Department, Faculty of Medicine, Baskent University, Istanbul Hospital, Turkey

### **References**


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#### **Chapter 4 Provisional chapter**

#### **Left Ventricular Noncompaction Left Ventricular Noncompaction**

Ana G. Almeida Ana G. Almeida

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Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/66291

#### **Abstract**

Left ventricular noncompaction (LVNC) is accepted as an unclassified (the American Heart Association) or a genetic cardiomyopathy (the European Society of Cardiology), but some argue that this phenotype may be a morphologic trait shared by different cardiomyopathies. This chapter covers the state of the art on the pathology, underlying mechanisms, its clinical manifestations, and diagnosis and treatment modalities of LVNC. LVNC may be defined as follows: an inner non‐compacted layer with prominent left ventricular trabeculae and deep intertrabecular recesses and a thin outer compacted layer. Mechanisms are still debatable, with the hypothesis of compaction arrest during embryogenesis as the most accepted theory. Genetic data support LVNC as a distinct cardiomyopathy, although evidence for LVNC as a shared morphological trait is not ruled out, since LVNC may be associated with other cardiomyopathies, congenital heart diseases and in some cases may be acquired. Diagnosis is based on imaging and may be confirmed by the use of genetics. Clinical picture and prognosis and the management options are discussed.

**Keywords:** cardiomyopathy, Noncompaction, Echocardiography, cardiovascular magnetic resonance, prognosis

### **1. Introduction**

Left ventricular noncompaction (LVNC) is a myocardial disorder that has been thought to occur due to the failure of left ventricle (LV) compaction during embryogenesis, leading to distinct morphological characteristics in the ventricular chamber [1]. In its first description, about 80 years ago, LVNC occurred in association with complex congenital heart diseases. More recently, an isolated form of LVNC was described [2], followed by many other reports. The involvement of the right ventricle in the noncompaction process has been increasingly

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© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

identified, and the condition is now included among the cardiomyopathies, but currently there is an intense debate whether LVNC is a distinct entity or a trait common to several cardiac conditions [3].
