REMODEL: Hypertensive Heart Disease
REMODEL: Hypertensive Heart Disease
Hypertension and aortic stenosis are the two leading conditions that cause thickening of the
 heart muscles (left ventricular hypertrophy). Left ventricular hypertrophy is initially
 adaptive to maintain optimal heart function. Ultimately, heart failure occurs as a result of
 progressive muscle cell death and scarring (myocardial fibrosis). Dedicated techniques using
 cardiovascular magnetic resonance imaging (MRI) and novel high-sensitivity cardiac troponin
 blood assays are potential markers to detect myocardial fibrosis. Although
 hypertension-related heart disease is very common in Singapore, the significance of
 myocardial fibrosis is not well understood. In this study, the significance of myocardial
 fibrosis in 500 patients with hypertension would be investigated. This will be the largest
 study using state-of-the-art MRI to examine the importance of myocardial fibrosis in
 hypertensive heart disease.
According to the National Health Survey in 2010, more than 50% of adults between 60-69 years
 old in Singapore had hypertension. As the population ages and life expectancy continues to
 increase, an increasing incidence of hypertensive heart disease would be expected. Similar to
 aortic stenosis, left ventricular hypertrophy in patients with hypertension was associated
 with adverse cardiovascular outcome, independent of traditional risk factors including
 peripheral blood pressure. Unlike aortic stenosis (a condition with fixed obstruction),
 arterial hypertension is dynamic and with effective medical therapy, left ventricular
 hypertrophy can regress and outcome will improve. As such, contemporary guidelines recommend
 more aggressive blood pressure control in patients with hypertension and left ventricular
 hypertrophy. However, the correlation between arterial pressure and left ventricular mass is
 weak, particularly in treated individuals. Coupled with the inherent limitations of measuring
 peripheral blood pressure, it is clear that using arterial pressure to monitor progression or
 assess treatment response in patients with hypertensive heart disease is not optimal.

 Without timely and appropriate therapies, left ventricular hypertrophy will become
 progressively maladaptive and ultimately the heart fails. Whilst heart failure is more
 commonly known by the signs and symptoms related to impaired systolic ejection fraction,
 heart failure with preserved ejection fraction is an increasingly recognized complex entity
 characterized by signs and symptoms of heart failure in the presence of preserved ejection
 fraction. To date, therapies that improve outcomes in heart failure with reduced ejection
 fraction have not shown similar benefits in patients with heart failure and preserved
 ejection fraction. There is no single explanation for these negative findings, but one
 potential reason may relate to the heterogeneity of patients recruited into these trials, and
 thus supporting a more targeted approach to specific phenotypes rather than a standard
 treatment strategy for all patients.

 Therefore, a focus on the transition from compensatory left ventricular hypertrophy to
 ventricular decompensation is crucial not only in furthering our understanding of the
 pathophysiology of hypertensive heart disease, but also instrumental in designing future
 trials. Small studies had reported replacement myocardial fibrosis in patients with
 hypertension. But these studies were small and unable to establish determinants associated
 with myocardial fibrosis. Unlike the increasing evidence of myocardial fibrosis in aortic
 stenosis, the prognosis associated with myocardial fibrosis in patients with hypertension is
 currently not known. Although there is promising data suggesting regression in myocardial
 fibrosis with certain antihypertensive therapies, the effects of myocardial fibrosis
 regression on long-term outcome is not known. As discussed earlier, other than relying on
 peripheral blood pressure, there are no biomarkers to monitor response of antihypertensive
 therapy on regression of left ventricular mass and myocardial fibrosis.

 Our investigators would establish a paradigm to demonstrate the significance of myocardial
 fibrosis in hypertensive heart disease; and examine other biomarkers associated with
 myocardial fibrosis and myocyte death that have high potential of translating into clinical
 application to monitor treatment response.
Inclusion Criteria:

 1. 21 years and over

 2. Physician diagnosed essential hypertension, on at least 1 medication for blood
 pressure control

 3. Newly diagnosed hypertension: systolic blood pressure 140mmHg or greater (diastolic
 blood pressure 90mmHg or greater) on at least 2 office visits (Weber 2013) and not
 started on any anti hypertensive medications at time of ambulatory blood pressure
 monitoring

 4. Resistant hypertension: persistent systolic blood pressure 140mmHg or greater
 (diastolic blood pressure 90mmHg or greater) despite on at least 3 anti-hypertensive
 medications (Jennings 2013; Weber 2013)

 Exclusion Criteria:

 1. Known secondary hypertension: renal causes (renal artery stenosis, chronic renal
 failure); endocrine causes (aldosterone excess, pheochromocytoma, cushing's syndrome,
 hyperthyroidism); cardiac causes (coarctation of the aorta)

 2. Contraindications to cardiovascular magnetic resonance: implantable devices, cerebral
 aneurysm clips, cochlear implants, renal impairment (GRF <30ml/min/1.73m2),
 claustrophobia and women who are pregnant or breast-feeding

 3. Limited life expectancy

 4. On-going unstable medical conditions: hypertensive crisis, acute coronary syndromes or
 acute heart failure

 5. History of coronary artery disease, ischemic heart disease

 6. History of transient ischemic attacks or cerebrovascular events

 7. History of atrial fibrillation

 8. History of heart failure