Donald Clark

Resistant Hypertension and Aldosterone: An Update

Resistant hypertension (RHTN) is defined as a blood pressure remaining above goal despite the concurrent use of 3 antihypertensive medications of different classes, including, ideally a diuretic. RHTN is an important health problem with a prevalence rate expected to increase as populations become older, more obese, and at higher risk of having diabetes and chronic kidney disease, all of which are important risk factors for development of RHTN. The role of aldosterone has gained increasing recognition as a significant contributor to antihypertensive treatment resistance. In prospective studies, the prevalence of primary aldosteronism (PA) has ranged from 14%-21% in patients with RHTN, which is considerably higher than in the general hypertensive population. Furthermore, marked antihypertensive effects are seen when mineralocorticoid antagonists are added to the treatment regimen of patients with RHTN, further supporting aldosterone excess as an important cause of RHTN. A close association exists between hyperaldosteronism, RHTN, and obstructive sleep apnea (OSA) based upon recent studies which indicate that OSA is worsened by aldosterone-mediated fluid retention. This interaction is supported by preliminary data which demonstrates improvement in OSA severity after treatment with spironolactone.

Magnetic Resonance Imaging With 3-Dimensional Analysis of Left Ventricular Remodeling in Isolated Mitral Regurgitation Implications Beyond Dimensions

Background— Although surgery is indicated in patients with mitral regurgitation (MR) when left ventricular (LV) end-systolic (LVES) dimension is >40 mm, LV ejection fraction may decrease after mitral valve surgery. We hypothesize that significant LV remodeling before surgery is not reflected by standard echocardiographic parameters measured at the base of the heart. Methods and Results— Ninety-four patients (age, 54±11 years; 38% female) with degenerative isolated MR underwent cine magnetic resonance imaging with tissue tagging and 3-dimensional analysis. In 51 control subjects (age, 44±14 years; 53% female), the relation between LVES volume (LVESV) and LVES dimension was quadratic, whereas in 94 MR patients, this relation was cubic, indicating a greater increase in LVESV per LVES dimension among MR patients. Moreover, magnetic resonance imaging LVESV from summated serial short-axis slices was significantly greater than LVESV assessed with the Bullet formula in MR patients, attributed to a more spherical remodeling distal to the tips of the papillary muscles (P<0.001). Thirty-five patients underwent mitral valve repair per current guideline recommendations. LV ejection fraction decreased from 61±7% to 54±8% (P<0.0001) and maximum shortening decreased significantly below normal at 1 year postoperatively (P<0.0001). Despite normalization of LV stroke volume and LV end-diastolic volume/mass ratio, there was a persistent significant increase in distal LVES 3-dimensional radius/wall thickness ratio and LVESV index after surgery. Conclusions— Despite apparently preserved LVES dimension, MR patients demonstrate significant spherical mid to apical LVES remodeling that contributes to higher LVESV than predicted by standard geometry-based calculations. Decreased LV strain after surgery suggests that a volumetric analysis of LV remodeling and function may be preferred to evaluate disease progression in isolated MR.

Aldosterone receptor antagonists: current perspectives and therapies.

Aldosterone is a downstream effector of angiotensin II in the renin–angiotensin–aldosterone system and binds to the mineralocorticoid receptor. The classical view of aldosterone primarily acting at the level of the kidneys to regulate plasma potassium and intravascular volume status is being supplemented by evidence of new “off-target” effects of aldosterone in other organ systems. The genomic effects of aldosterone are well known, but there is also evidence for non-genomic effects and these recently identified effects of aldosterone have required a revision in the traditional view of aldosterone’s role in human health and disease. The aim of this article is to review the biological action of aldosterone and the mineralocorticoid receptor leading to subsequent physiologic and pathophysiologic effects involving the vasculature, central nervous system, heart, and kidneys. Furthermore, we outline current evidence evaluating the use of mineralocorticoid receptor antagonists in the treatment of primary aldosteronism, primary hypertension, resistant hypertension, obstructive sleep apnea, heart failure, and chronic kidney disease.

Recent Advancements in the Treatment of Resistant Hypertension

Abstract The 2008 Scientific statement from the American Heart Association defined resistant hypertension as blood pressure remaining above goal (< 140/90 mm Hg for the general population and < 130/80 mm Hg for patients with diabetes or renal disease) despite the concurrent use of optimal doses of 3 antihypertensive agents of different classes, ideally including a diuretic. Since then, there has been increasing recognition and characterization of patients with resistant hypertension and development of treatment strategies to treat this high–risk population. The role of aldosterone in resistant hypertension has gained increasing recognition. In particular, there has been development of a strong body of evidence for the use of spironolactone as a highly effective antihypertensive agent. Furthermore, there is increasing evidence to link aldosterone with both resistant hypertension and obstructive sleep apnea, with preliminary studies suggesting that aldosterone antagonists may potentially be effective in treating both conditions. Finally, recent work has directed increased attention toward novel invasive strategies for the treatment of resistant hypertension, specifically baroreflex activation therapy with carotid stimulation and percutaneous renal artery denervation. Initial randomized controlled trials have shown that both of these methods may be used to safely lower blood pressure, thereby providing exciting and promising new tools in the armamentarium of options to treat resistant hypertension.

An argument for reviving the disappearing skill of cardiac auscultation.

Three case scenarios show how the clinical examination can complement echocardiography in the evaluation of valvular heart disease.

Submassive Pulmonary Embolism Where’s the Tipping Point?

Information about a real patient is presented in stages (boldface type) to expert clinicians (Drs Louis J. Dell’Italia and David C. McGiffin) who respond to the information, sharing his or her reasoning with the reader (regular type). A discussion by the authors follows. A 67-year-old black woman presents to the emergency department with a 1-day history of dyspnea, which began the previous morning initially with moderate exertion now progressing to dyspnea at rest. She denies chest pain, cough, palpitations, nausea, diaphoresis, lower extremity swelling, paroxysmal nocturnal dyspnea, orthopnea, presyncope, or syncope. Her medical history is notable for hypertension, diabetes mellitus, and hypothyroidism. Her medications include metoprolol tartrate 12.5 mg twice daily, metformin 1000 mg twice daily, levothyroxine 25 μg daily, and estradiol 1 mg daily for symptomatic management of hot flashes. She lives alone and is a retired schoolteacher. She does not smoke, drink alcohol, or use illicit drugs. Family history is not significant. Travel history is notable for round-trip plane flight from Alabama to Utah, arriving home 2 days previously. On physical examination her temperature is 98.4°F, pulse is 94 beats/min, blood pressure is 112/55 mm Hg in the right arm, 110/58 mm Hg in the left arm, respiratory rate 26 breaths/min, and oxygen saturation 90% on room air. She is an obese black woman (body mass index 32 kg/m2) in mild distress secondary to shortness of breath. Jugular venous pressure is estimated at 14 cm H20. Lungs are clear to auscultation. The heart rhythm is regular with a normal S1 and S2. No murmurs, rubs, or gallops are appreciated. Peripheral pulses are brisk and symmetrical with trace pretibial pitting edema. Abdominal examination is benign. Dr Louis J. Dell’Italia: This patient presents with a 24-hour history of dyspnea progressing from symptoms with exertion to now occurring …

MORTALITY OUTCOMES FOR SURGICAL PULMONARY EMBOLECTOMY FOR HIGH-RISK PULMONARY EMBOLISM: A COMPREHENSIVE META-ANALYSIS

Untreated high-risk pulmonary embolism (PE) is associated with a mortality rate as high as 60%. Surgical pulmonary embolectomy (SPE) is an efficacious treatment but outcomes data regarding this approach are limited. We sought to characterize mortality outcomes for patients with high-risk PE

ROLE OF INFERIOR VENA CAVA FILTERS IN PATIENTS UNDERGOING CATHETER-BASED TREATMENT OF ACUTE PULMONARY EMBOLISM: A COMPREHENSIVE META-ANALYSIS

Catheter-based treatment (CBT) is an evolving therapeutic strategy for acute pulmonary embolism (PE). We previously described in-hospital mortality rates among patients with acute PE undergoing CBT (1). Inferior vena caval (IVC) filters are often placed to prevent recurrent PE. We hypothesized that

MORTALITY OUTCOMES FOR CATHETER-BASED EMBOLECTOMY FOR TREATMENT OF ACUTE PULMONARY EMBOLISM: A COMPREHENSIVE META-ANALYSIS

Untreated high-risk pulmonary embolism is associated with a high mortality rate. Catheter-based treatment of pulmonary embolism may provide effective immediate treatment without the inherent bleeding risks of systemic thrombolysis, but outcomes data regarding this approach are limited. We searched

Cardiac device-related invasive aspergilloma assessed by live/real time three-dimensional transthoracic echocardiography.

Cardiac device–related infection caused by Aspergillus species is a rare finding associated with high mortality. Prompt recognition and treatment is imperative, but difficult as blood cultures are often negative and diagnosis requires a high index of suspicion. Live/real time three‐dimensional transthoracic echocardiography (3DTTE) provides incremental knowledge in the characterization of valvular vegetations. Here, we provide a detailed description of an invasive cardiac device–related infection caused by Aspergillus fumigatus using 3DTTE. Findings described here highlight the role for 3DTTE in the prompt diagnosis of invasive cardiac Aspergillus infections as well as surgical planning in such cases.