Nikolaos Tzemos

Adverse Cardiovascular Effects of Acute Salt Loading in Young Normotensive Individuals

We sought to explore the effects of salt loading in young normotensives on vascular endothelial function, echocardiographic left ventricular diastolic function, and electrocardiographic QT dispersion. Sixteen healthy normotensive male volunteers were randomized in a double-blind crossover fashion to 5-day treatment periods with either placebo or salt tablets (200 mmol/d of sodium) separated by a 2-week washout period. Throughout the study the volunteers were asked to maintain a low-salt diet. Forearm venous occlusion plethysmography and intraarterial infusions of acetylcholine (ACh), sodium nitroprusside (SNP), and NG-monomethyl-l-arginine (L-NMMA) were used to assess vascular reactivity. Baseline and postsalt loading 12-lead ECGs and echocardiograms were also obtained. Twenty-four-hour ambulatory systolic blood pressure rose (117±11 to 121±8 mm Hg) significantly with salt loading. The endothelium-dependent responses to ACh were significantly blunted with salt compared to placebo (&Dgr;FBF% 403 [50] versus 296 [31]; P<0.05) and L-NMMA (&Dgr;FBF% −47.2 [4] versus −31 [3]; P<0.01). In contrast, the endothelium-independent response to SNP was not different between treatments. Color M-mode flow propagation velocity (CMMFPV), a preload index of left ventricular diastolic function, was significantly reduced with salt (64 [6] versus 59 [16] cm/s; P<0.05) suggesting increased ventricular stiffness. QT dispersion was also significantly increased with salt (58 [16] versus 48 [17] ms; P=0.02). Salt loading impaired vascular endothelial function, left ventricular mechanical relaxation, and electric repolarization in young healthy normotensives.

Exercise blood pressure and endothelial dysfunction in hypertension

Background:  Hypertensive patients with persistent endothelial dysfunction have adverse cardiovascular prognosis. However, current methods aimed to assess endothelial dysfunction in those patients who possess clinical applicability. We hypothesised that such individuals could potentially be identified by an exaggerated systolic blood pressure (BP) response to a submaximal exercise.

Bicuspid Aortic Valve Disease: A Comprehensive Review

Bicuspid aortic valve is the commonest congenital cardiac abnormality in the general population. This paper article will discuss our current knowledge of the anatomy, pathophysiology, genetics, and clinical aspects of bicuspid aortic valve disease.

Valsartan Improves Endothelial Dysfunction in Hypertension: A Randomized, Double‐Blind Study

Endothelial dysfunction can predict cardiac outcomes in hypertension and reversing this abnormality has become an attractive therapeutic objective. We tested the hypothesis that blocking the angiotensin type 1 (AT1) receptor with valsartan in comparison with amlodipine would lead to an improvement in forearm resistance artery endothelial dysfunction. In total, 25 hypertensive subjects (mean age 60 years, SD 8) with a mean daytime ambulatory blood pressure (BP) of 154 (10)/97 (6) mmHg were randomized following a 3-week placebo run-in period to a double-blind, crossover trial of 16-week treatment periods with either valsartan or amlodipine, separated by a 3-week washout period. Intra-arterial infusions of acetylcholine (ACh) and NG-monomethyl-L-arginine (L-NMMA) were used to assess stimulated and basal endothelium-dependent nitric oxide (NO) release, respectively. Coinfusion of ACh and L-NMMA was employed to investigate the existence of an NO-independent vasodilatory pathway. Valsartan and amlodipine each lowered the clinical BP to the same extent (139 [7]/87 [6] and 139 [11]/89 [4] mmHg, respectively). The vasodilatory response to ACh was significantly increased with valsartan (maximal percentage change in forearm blood flow (max. ΔFBF%) 301 [47] vs. 185 [34], mean [SEM]; P < 0.05) as compared with placebo, but remained unchanged with amlodipine. Both valsartan and amlodipine similarly increased the vasoconstrictive response to L-NMMA (max. ΔFBF%–43 [5], −42 [5], respectively, vs. –26 [3] baseline; P < 0.001). The vasodilatory response after coinfusion of ACh and L-NMMA was significantly (P < 0.05) enhanced only with valsartan. Valsartan reserved peripheral endothelial dysfunction through both NO-dependent and -independent pathways, while for the same degree of BP control, amlodipine had only a partial effect on NO bioactivity.

Reversible hypertension following coeliac disease treatment: the role of moderate hyperhomocysteinaemia and vascular endothelial dysfunction.

The vascular endothelium maintains a relatively vasodilated state via the release of nitric oxide (NO), a process that could be disrupted by hyperhomocysteinaemia. Since endothelial dysfunction is associated with increased systemic vascular resistance that is the hallmark of sustained arterial hypertension, we hypothesised that in patients with both hypertension and coeliac disease with hyperhomocysteinaemia (via malabsorption of essential cofactors), treatment of the latter disease could improve blood pressure (BP) control. A single patient with proven sustained hypertension and newly-diagnosed coeliac disease had baseline and post-treatment BP and endothelial function assessed by ambulatory BP monitoring (ABPM) and brachial artery forearm occlusion plethysmography respectively. This 49 year-old woman had uncomplicated sustained hypertension proven on repeated ABPM carried out 6 weeks apart (daytime mean 151/92 mm Hg and 155/95 mm Hg), and sub-clinical coeliac disease (gluten-sensitive enteropathy). Initial assessments revealed raised homocysteine levels with low normal vitamin B12 level. It was likely that she had impaired absorption of essential cofactors for normal homocysteine metabolism. She adhered to a gluten-free diet and was give oral iron, folate and B6 supplementations as well as B12 injections for 3 months. Her BP had improved by 6 months and normalised by 15 months (daytime ABPM mean 128/80 mm Hg). There was parallel restoration of normal endothelial function with normalisation of her homocysteine levels. These observations suggest that sub-clinical coeliac disease related hyperhomocysteinaemia might cause endothelial dysfunction, potentially giving rise to a reversible form of hypertension. In addition, this case study supports the notion that irrespective of aetiology, endothelial dysfunction may be the precursor of hypertension. This highlights the need to resolve co-existing vascular risk factors in patients with hypertension.

Endothelial dysfunction in human essential hypertension

Although the endothelium has a number of important functions, the term endothelial dysfunction is commonly used to describe impairment in its vasodilatory capacity. It is increasingly recognized that this is related to hypertension, although whether it predates essential hypertension or is a consequence of it is still unknown. In this review, we explore the mechanisms of endothelial dysfunction in essential hypertension, its prognostic significance and methods of pharmacological reversal.

The Combined Incremental Prognostic Value of LVEF, Late Gadolinium Enhancement, and Global Circumferential Strain Assessed by CMR.

OBJECTIVES This study aimed to assess the incremental prognostic value of global circumferential strain (GCS), as measured using cardiac magnetic resonance (CMR) tagging, in addition to baseline clinical characteristics, left ventricular ejection fraction (LVEF), and late gadolinium enhancement (LGE), in the prediction of major adverse cardiovascular events (MACE) in an unselected cohort of patients. BACKGROUND LVEF is a powerful predictor of mortality and is used for guiding treatment decisions. It is, however, subject to limitations. The value of GCS measured by CMR tagging in patients with suspected cardiac disease has not been fully explored despite its being considered as the gold standard noninvasive method of assessment of LV deformation. METHODS We prospectively evaluated data from 539 consecutive patients referred for CMR who underwent a CMR protocol that included cine imaging, tagging, and LGE. The primary endpoint was the prevalence of MACE, defined as a composite of all-cause mortality, heart failure-related hospitalization, and aborted sudden cardiac death. RESULTS MACE occurred in 62 of 539 patients (11.5%) over a mean follow-up period of 2.2 years. History of ischemic heart disease (IHD) and beta-blocker use were both significant clinical predictors of adverse outcomes. All 3 CMR parameters were significant multivariate predictors of the primary outcome when added to significant clinical predictors (LVEF, hazard ratio [HR]: 0.96 [95% confidence interval [CI]: 0.94 to 0.99; p = 0.005]; presence of LGE, HR: 2.07 [95% CI: 1.03 to 4.14; p = 0.04]; GCS, HR: 1.11 [95% CI: 1.02 to 1.21; p = 0.041]). Global chi-square increased significantly with the addition of both LGE and GCS. Both the presence of LGE and reduced GCS had independent prognostic value in the overall cohort. Patients with LVEF ≥35% but LGE present and reduced GCS had a poor outcome similar to that in those with LVEF <35%. CONCLUSIONS We found, in a large-scale cohort of patients, that GCS, in addition to clinical variables, LVEF, and LGE, had incremental independent prognostic value. This measure could provide further risk stratification, especially in patients with mild LV impairment.

Exaggerated Exercise Blood Pressure Response and Future Cardiovascular Disease

Exaggerated blood pressure (BP) response to exercise predicts future hypertension. However, there is considerable lack of understanding regarding the mechanism of how this abnormal response is generated, and how it relates to the future establishment of cardiovascular disease. The authors studied 82 healthy male volunteers without cardiovascular risk factors. The participants were categorized into two age‐matched groups depending on their exercise systolic BP (ExSBP) rise after 3 minutes of exercise using a submaximal step test: exaggerated ExSBP group (hyper‐responders [peak SBP ≥180 mm Hg]) and low ExSBP responder group (hypo‐responders [peak SBP <180 mm Hg]). Forearm venous occlusion plethysmography and intra‐arterial infusions of acetylcholine (ACh), NG‐monomethyl‐L‐arginine (L‐NMMA), sodium nitroprusside (SNP), and norepinephrine (NE) were used to assess vascular reactivity. Proximal aortic compliance was assessed with ultrasound, and neurohormonal blood sampling was performed at rest and during peak exercise. The hyper‐responder group exhibited a significantly lower increase in forearm blood flow (FBF) with ACh compared with the hypo‐responder group (ΔFBF 215% [14] vs 332.3% [28], mean [standard error of the mean]; P<.001), as well as decreased proximal aortic compliance. The vasoconstrictive response to L‐NMMA was significantly impaired in the hyper‐responder group in comparison to the hypo‐responder group (ΔFBF −40.2% [1.6] vs −50.2% [2.6]; P<.05). In contrast, the vascular response to SNP and NE were comparable in both groups. Peak exercise plasma angiotensin II levels were significantly higher in the hyper‐responder group (31 [1] vs 23 [2] pg/mL, P=.01). An exaggerated BP response to exercise is related to endothelial dysfunction, decreased proximal aortic compliance, and increased exercise‐related neurohormonal activation, the constellation of which may explain future cardiovascular disease.

Is reversal of endothelial dysfunction still an attractive target in modern cardiology

Although the endothelium has a number of important functions, the term endothelial dysfunction is commonly used to describe impairment in its vasodilatory capacity. There have been numerous studies evaluating the relationship between endothelial dysfunction and cardiovascular disease, however assessment of endothelial function is perhaps still primarily thought of as a research tool and has not reached widespread clinical acceptance. In this review we explore the relationship between endothelial dysfunction and cardiovascular disease, its prognostic significance, methods of pharmacological reversal of endothelial dysfunction, and ask the question, is reversal of endothelial dysfunction still an attractive target in modern cardiology?

LGE and NT-proBNP Identify Low Risk of Death or Arrhythmic Events in Patients With Primary Prevention ICDs

OBJECTIVES The aim of this study was to investigate whether late gadolinium enhancement (LGE) magnetic resonance imaging or N-terminal pro-B-type natriuretic peptide (NT-proBNP) could identify patients with a low risk of death or use of implantable cardioverter-defibrillator (ICD) in patients receiving a primary prevention ICD. BACKGROUND ICDs reduce mortality in patients with heart failure (HF), although two-thirds may never use their device. Current risk stratification, based on New York Heart Association functional class and left ventricular ejection fraction, still leads to implantation of ICDs in patients who may never need their device. METHODS We examined 157 patients with HF (61 with ischemic cardiomyopathy and 96 with dilated cardiomyopathy; mean age 50.5 years; 78% male) who underwent primary prevention defibrillator implantation. Presence and volume of LGE was measured before device implantation, and serum NT-proBNP level was measured before ICD implantation. The combined primary endpoint was cardiovascular death or appropriate ICD therapy (either appropriate shock or antitachycardia pacing). RESULTS The primary outcome occurred in 32 patients (20.4%) over a median follow-up period of 915 days. Percentage of LGE (hazard ratio [HR]: per 1% increase: 1.06; 95% confidence interval [CI]: 1.04 to 1.09; p < 0.001) and (ln) NT-proBNP (HR: 1.44; 95% CI: 1.04 to 1.98; p = 0.027) were predictors of death or appropriate ICD activation and remained significant when entered into multivariable analysis. When the cohort was stratified into tertiles based on LGE percentage and NT-proBNP, we were able to identify a low-risk group (event rate 3% per year, compared with the intermediate- and high-risk groups [6% and 10% per year, respectively]). CONCLUSIONS Both percentage of LGE and NT-proBNP were associated with higher risk of death or appropriate ICD activation. The use of these markers in combination may be useful in identifying individuals most likely to benefit from this costly intervention, and more specifically, in the identification of a group at lower risk in whom ICD implantation may be deferred.