Cardiovascular Diseases That Have Emerged From the Darkness

Abstract

It is important for both the patient and physician communities to have timely access to information recognizing rapid progress in the diagnosis and treatment of familiar but relatively uncommon cardiovascular diseases. Patients with 3 cardiovascular diseases (ie, hypertrophic cardiomyopathy, pulmonary arterial hypertension, and transthyretin (TTR) cardiac amyloidosis (ATTR)]), once considered rare without effective management options and associated with malignant prognosis, have now benefited substantially from the development of a variety of innovative therapeutic strategies. In addition, in each case, enhanced diagnostic testing has expanded the patient population and allowed for more widespread administration of contemporary treatments. In hypertrophic cardiomyopathy, introduction of implantable defibrillators to prevent sudden death as well as high-benefit:low-risk septal reduction therapies to reverse heart failure have substantially reduced morbidity and disease-related mortality (to 0.5% per year). For pulmonary arterial hypertension, a disease once characterized by a particularly grim prognosis, prospective randomized drug trials with aggressive single (or combined) pharmacotherapy have measurably improved survival and quality of life for many patients. In cardiac amyloidosis, development of disease-specific drugs can for the first time reduce morbidity and mortality, prominently with breakthrough ATTR-protein-stabilizing tafamidis. In conclusion, in less common and visible cardiovascular diseases, it is crucial to recognize substantial progress and achievement, given that penetration of such information into clinical practice and the patient community can be inconsistent. Diseases such as hypertrophic cardiomyopathy, pulmonary arterial hypertension, and ATTR cardiac amyloidosis, once linked to a uniformly adverse prognosis, are now associated with the opportunity for patients to experience satisfactory quality of life and extended longevity.

Keywords: amyloid; drug therapy; heart failure; hypertrophic cardiomyopathy; implantable cardioverter‐defibrillator; pulmonary hypertension; sudden death.

Figure 1. Hypertrophic cardiomyopathy: clinical spectrum and outcome.

FW, free wall; LA indicates left atrium; LV, left ventricle; LVOT, left ventricular outflow tract; RV, right ventricle; VS, ventricular septum; and VT/VF, ventricular tachycardia/ventricular fibrillation.

Figure 2. Constructed Kaplan‐Meier curves showing reduction in all‐cause mortality associated with contemporary treatment advances for 3 diseases.

A, Hypertrophic cardiomyopathy, current treatment vs prior eras., , , , B, Pulmonary arterial hypertension, current treatment vs pretreatment era., , , , , C, ATTR (transthyretin) cardiac amyloidosis, treatment with tafamidis vs conventional treatment.,

Figure 3. Timeline of clinical advances in hypertrophic cardiomyopathy (HCM).

ACC indicates American College of Cardiology; AHA, American Heart Association; CMR, cardiovascular magnetic resonance; ESC, European Society of Cardiology; and SAM, systolic anterior motion.

Figure 4. Pulmonary arterial hypertension (PAH): pathophysiology and outcome, showing an example of the severe primary abnormality of PAH from a patient with marked medial and intimal thickening and luminal narrowing of small pulmonary arteries.

mPAP indicates mean pulmonary arterial pressure; PAWP, pulmonary artery wedge pressure; PVR, pulmonary vascular resistance; and WU, Wood units.

Figure 5. Timeline of clinical advances in pulmonary hypertension.

AMBITION indicates Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension; IV, intravenous; mPAP, mean pulmonary artery pressure; PAH, pulmonary arterial hypertension; PHAROS, Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma; RCTs, randomized controlled trials; REVEAL, Registry to Evaluate Early and Long‐Term PAH Disease Management; SERAPHIN, Study With an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome; and WHO, World Health Organization

Figure 6. ATTR (transthyretin).

Pathophysiology of ATTR amyloid cardiomyopathy.

Figure 7. Timeline of clinical advances in TTR (transthyretin) cardiac amyloidosis.

99mTc‐PYP indicates technetium TC 99M pyrophosphate; hATTR, hereditary ATTR (transthyretin) cardiac amyloidosis; Val30met, variant in which methionine replaces valine at the 30th position of TTR protein (Portuguese variant); and Val122Ile, variant in which isoleucine replaces valine at the 112nd position of TTR protein.