Vasodilator Therapy In Patients Research Articles

Low Mean Perfusion Pressure Indexed to Body Surface Area is a Powerful Predictor of Poor Outcomes After Heart Transplantation in Patients With High Pre-Transplant Venous Pressure: A Clinical Study With Physiological Insights From Mathematical Modelling of Biventricular Heart Failure

The deleterious consequences of chronically elevated venous pressure in patients with profound right ventricular or biventricular dysfunction are well known, including renal and hepatic dysfunction, and volume overload. The only option for these patients, if they fail optimal medical treatment, is a heart transplant, as they are not candidates for left ventricular assist device therapy. Mean perfusion pressure (MPP) is important in the outcomes of critically ill patients with high venous pressure. The question arises whether MPP is important for the outcomes of heart transplants in patients with elevated pre-transplant venous pressure. Medical management of heart failure patients with reduced ejection fraction involves lowering the systemic afterload with vasodilators while awaiting a transplant. We hypothesised that when venous pressure is elevated prior to transplant, a substantial reduction in systemic arterial elastance (Ea) through vasodilation may significantly decrease MPP, resulting in compromised end-organ function and consequent unfavourable outcomes after heart transplantation. This study aims to investigate whether a low MPP serves as a risk factor for adverse outcomes in heart transplant recipients with high venous pressure. A retrospective analysis was conducted on 250 heart transplant recipients undergoing isolated heart transplantation at a single institution from October 2012 to March 2020. Right atrial pressure (RAP) of more than 15 mmHg was considered high. Additionally, Ea calculated as the ratio of end-systolic pressure to stroke volume, and MPP calculated as the difference between mean arterial pressure and RAP were considered in our analysis. The outcomes of transplantation were measured in terms of 90-day mortality and survival up to 7 years. High RAP was a significant risk factor for short-term and medium-term survival if Ea was low (<2.7 mmHg/mL, the median value). This group had 39.39% in-hospital mortality compared to 14.49% for RAP<15 mmHg (p∼0.005). When Ea was high, this difference in survival was not evident: 8% for RAP<15 mmHg vs 4.8% for RAP>15 mmHg (p∼0.550). This effect was mediated through a lower MPP, and the mortality due to lower MPP increased strikingly with higher body surface area (BSA). A negative correlation was observed between MPP indexed to BSA (MPPI) and the Model for End-Stage Liver Disease score (r∼-0.3580, p<0.0001) as well as creatinine (r∼-0.3551, p<0.0001). MPPI less than 40 mmHg/m2 was associated with poorer short-term (23.2% for MPPI<40 mmHg/m2 vs 7.1% for MPPI>40 mmHg/m2, p∼0.001) and medium-term survival. The impact of high RAP and low Ea on survival was evident even on medium-term follow-up; only 30% survival at 7 years follow-up for high RAP and low Ea vs 75% for RAP<15 mmHg (p∼0.0033). The acceptable blood pressure during vasodilator therapy in patients with high RAP needs to be higher, especially in those with higher BSA. MPPI less than 40 mmHg/m2 is a risk factor for survival, in the short and medium-term, after heart transplantation.

Pulmonary Hypertension in Interstitial Lung Disease: Updates in Disease, Diagnosis, and Therapeutics.

Pulmonary hypertension is a debilitating condition that frequently develops in the setting of interstitial lung disease, likely related to chronic alveolar hypoxemia and pulmonary vascular remodeling. This disease process is likely to be identified more frequently by providers given recent advancements in definitions and diagnostic modalities, and provides practitioners with emerging opportunities to improve patient outcomes and quality of life. Despite years of data suggesting against the efficacy of pulmonary vasodilator therapy in patients with pulmonary hypertension due to interstitial lung disease, new data have emerged identifying promising advancements in therapeutics. The authors present to you a comprehensive review of pulmonary hypertension in interstitial lung disease, reviewing our current understanding of pathophysiology, updates in diagnostic approaches, and highlights of recent clinical trials which provide an effective approach for medical management.

Non-invasive detection of severe PH in lung disease using magnetic resonance imaging.

Severe pulmonary hypertension (mean pulmonary artery pressure ≥35 mmHg) in chronic lung disease (PH-CLD) is associated with high mortality and morbidity. Data suggesting potential response to vasodilator therapy in patients with PH-CLD is emerging. The current diagnostic strategy utilises transthoracic Echocardiography (TTE), which can be technically challenging in some patients with advanced CLD. The aim of this study was to evaluate the diagnostic role of MRI models to diagnose severe PH in CLD. 167 patients with CLD referred for suspected PH who underwent baseline cardiac MRI, pulmonary function tests and right heart catheterisation were identified. In a derivation cohort (n = 67) a bi-logistic regression model was developed to identify severe PH and compared to a previously published multiparameter model (Whitfield model), which is based on interventricular septal angle, ventricular mass index and diastolic pulmonary artery area. The model was evaluated in a test cohort. The CLD-PH MRI model [= (-13.104) + (13.059 * VMI)-(0.237 * PA RAC) + (0.083 * Systolic Septal Angle)], had high accuracy in the test cohort (area under the ROC curve (0.91) (p < 0.0001), sensitivity 92.3%, specificity 70.2%, PPV 77.4%, and NPV 89.2%. The Whitfield model also had high accuracy in the test cohort (area under the ROC curve (0.92) (p < 0.0001), sensitivity 80.8%, specificity 87.2%, PPV 87.5%, and NPV 80.4%. The CLD-PH MRI model and Whitfield model have high accuracy to detect severe PH in CLD, and have strong prognostic value.

Prognostic Impact of Chronic Vasodilator Therapy in Patients With Vasospastic Angina.

BackgroundChronic vasodilator therapy with long‐acting nitrate is frequently used to treat vasospastic angina. However, the clinical benefits of this approach are controversial. We investigated the prognostic impact of vasodilator therapy in patients with vasospastic angina from the multicenter, prospective VA‐KOREA (Vasospastic Angina in KOREA) registry.Methods and ResultsWe analyzed data from 1895 patients with positive intracoronary ergonovine provocation test results. The patients were divided into 4 groups: no vasodilator (n=359), nonnitrate vasodilator (n=1187), conventional nitrate (n=209), and a combination of conventional nitrate and other vasodilators (n=140). The primary end point was a composite of cardiac death, acute coronary syndrome, and new‐onset arrhythmia at 2 years. Secondary end points were the individual components of the primary end point, all‐cause death, and rehospitalization due to recurrent angina.The groups did not differ in terms of the risk of the primary end point. However, the acute coronary syndrome risk was significantly higher in the conventional nitrate (hazard ratio [HR], 2.49; 95% CI, 1.01–6.14; P=0.047) and combination groups (HR, 3.34; 95% CI, 1.15–9.75, P=0.027) compared with the no‐vasodilator group, as assessed using the inverse probability of treatment weights. Subgroup analyses revealed prominent adverse effects of nitrate in patients with an intermediate positive ergonovine provocation test result and in those with low Japanese Coronary Spasm Association scores.ConclusionsLong‐acting nitrate‐based chronic vasodilator therapy was associated with an increased 2‐year risk of acute coronary syndrome in patients with vasospastic angina, especially in low‐risk patients.

Correction of High Afterload Improves Low Cardiac Output in Patients Supported on Left Ventricular Assist Device Therapy.

There is a paucity of data describing the invasive assessment of afterload and influence on cardiac output in patients supported on left ventricular assist device (LVAD) therapy. From 2015 to 2018, patients on LVAD therapy were evaluated with simultaneous left/right heart catheterization ramp study for speed optimization. Hemodynamic parameters from 31 patients without significant aortic insufficiency were analyzed. Mean central aortic pressure (MAP) was elevated at 87 ± 13 mm Hg at baseline. No direct association between MAP and cardiac index (CI) was found (r = 0.11, p = 0.20). However, variable MAP provided vastly different patterns of cardiac output response to speed increments (positive correlation, p = 0.047 for MAP <80 mm Hg; negative trend, p = 0.25 for MAP > 100 mm Hg). Patients noted to be hypertensive (MAP > 90, n = 8) received nitrate therapy and experienced both improvement in biventricular filling pressures and a mean increase in CI from 2.4 to 2.9 L/min/m2 (+22%, p = 0.04) at a fixed revolutions per minute. High afterload is common in patients on LVAD therapy, is associated with poor response to ramp, and is ameliorated by nitrates. These findings serve as a foundation to evaluate the dynamic effects of high afterload and chronic vasodilator therapy in patients with durable LVADs.

Tolerability, Safety, and Hemodynamics of Sacubitril-Valsartan in Acutely Decompensated Heart Failure Patients with Cardiogenic Shock

Introduction A recent randomized clinical study established the safety of the angiotensin receptor-neprilysin inhibitor (ARNI), sacubitril-valsartan (S/V), in patients hospitalized with acute decompensated heart failure after achieving hemodynamic stability. Transitioning patients in cardiogenic shock managed with pulmonary artery catheters directly from intravenous vasoactive (i.e. vasodilators or inotropes) drugs to S/V represents a potentially novel use for ARNIs. The tolerability and hemodynamic characteristics of S/V in patients with cardiogenic shock has not been previously established. Methods A single-center, retrospective analysis of all patients with heart failure and a reduced ejection fraction (HFrEF) (EF Results Twenty-two patients in the CICUs with HFrEF were started on S/V. The baseline characteristics, pertinent lab values, and hemodynamic profile (CI, SVR), are presented (Image 1). Ninety-five percent (n=21) of patients were on either of sodium nitroprusside, milrinone, dobutamine, or a combination these agents, at the time of initiation. Seventy-seven percent (n=17/22) patients were discharged on S/V with improved hemodynamics (Image 1,2). Hypotension was the most common reason for discontinuation (n=4) however one patient had both acute kidney injury and hypotension (n=1); no patients had hyperkalemia or death (n=0) (Image 2). Two of five intolerant patients were initiated on moderate (49-51) dose S/V. Conclusions The novel use S/V as oral vasodilator therapy in patients with cardiogenic shock shows favorable hemodynamic impact and tolerability. Long term tolerability and outcomes are required.

High Afterload Driving Poor Cardiac Output in LVAD Patients is Rectified with Nitrate Therapy

Purpose There is a paucity of data describing influences on cardiac output in patients supported on LVAD therapy. We describe, for the first time, the independent impact of afterload on cardiac output in the LVAD population. Methods Between 2015 and 2018, 54 patients on LVAD therapy were evaluated with simultaneous left and right heart catheterization ramp study. All patients with significant aortic regurgitation or device malfunction/thrombosis were excluded. Hemodynamic parameters from the 30 remaining patients undergoing speed optimization were analyzed. Results Mean central aortic pressure (MAP) was 87 ± 13 mmHg at baseline and correlated significantly with RPM for each pump type (R > 0.24, p ≤ 0.05 for all). No association between MAP or RPM and cardiac index (CI) was found. However, there was a significant correlation between systemic vascular resistance (SVRi) and CI (R = -0.76, p 90, n=8) received nitrate therapy and experienced a mean increase in cardiac index from 2.3 L/min/m2 to 2.8 L/min/m2 (mean increase of 23%) at a given RPM, validating the physiologic afterload findings. Conclusion Afterload as measured by LV-EA or SVRi negatively influences cardiac output in LVAD therapy and is ameliorated by nitrates. These findings serve as a foundation to evaluate the dynamic effects of high afterload and chronic vasodilator therapy in patients with durable LVADs.

Temporal evolution of vasospasm and clinical outcome after intra-arterial vasodilator therapy in patients with aneurysmal subarachnoid hemorrhage.

Intra-arterial (IA) vasodilator therapy is one of the recommended treatments to minimize the impact of aneurysmal subarachnoid hemorrhage-induced cerebral vasospasm refractory to standard management. However, its usefulness and efficacy is not well established. We evaluated the effect IA vasodilator therapy on middle cerebral artery blood flow and on discharge outcome. We reviewed records for 115 adults admitted to Neurointensive Care Unit to test whether there was a difference in clinical outcome (discharge mRS) in those who received IA infusions. In a subset of 19 patients (33 vessels) treated using IA therapy, we tested whether therapy was effective in reversing the trends in blood flow. All measures of MCA blood flow increased from day -2 to -1 before infusion (maximum Peak Systolic Velocity (PSV) 232.2±9.4 to 262.4±12.5 cm/s [p = 0.02]; average PSV 202.1±8.5 to 229.9±10.9 [p = 0.02]; highest Mean Flow Velocity (MFV) 154.3±8.3 to 172.9±10.5 [p = 0.10]; average MFV 125.5±6.3 to 147.8±9.5 cm/s, [p = 0.02]) but not post-infusion (maximum PSV 261.2±14.6 cm/s [p = .89]; average PSV 223.4±11.4 [p = 0.56]; highest MFV 182.9±12.4 cm/s [p = 0.38]; average MFV 153.0±10.2 cm/s [p = 0.54]). After IA therapy, flow velocities were consistently reduced (day X infusion interaction p<0.01 for all measures). However, discharge mRS was higher in IA infusion group, even after adjusting for sex, age, and admission grades. Thus, while IA vasodilator therapy was effective in reversing the vasospasm-mediated deterioration in blood flow, clinical outcomes in the treated group were worse than the untreated group. There is need for a prospective randomized controlled trial to avoid potential confounding effect of selection bias.

Coronary Artery Bypass Surgery in Left Main Disease with Idiopathic Artery Pulmonary Hypertension. Role of PGE Therapy

Introduction Idiopathic pulmonary hypertension (PAH) is a rare disease of unknown etiology that leads to the development of severe precapillary pulmonary hypertension [ 1 - 3 ], characterized by impaired regulation of both pulmonary hemodynamics and vascular growth.’ The responsiveness to vasodilator therapy in patients with PAH varies considerably [ 4 , 5 ]. Coronary artery bypass grafting (CABG) with extracorporeal circulation has a deleterious effect on lung tissues.

Efficacy of pulmonary vasodilator therapy in patients with functionally single ventricle.

This study retrospectively evaluated the effectiveness of pulmonary vasodilator therapy with bosentan (n = 14) and/ or sildenafil (n = 23) in 34 patients with a functionally single ventricle. Vasodilator therapy was initiated before the Fontan procedure in 18 patients and after the procedure in 16 patients. The reasons for vasodilator treatment included high pulmonary artery pressure or pulmonary vascular resistance (n = 8), high central venous pressure after the Fontan or bidirectional Glenn procedure (n = 7), and ventilatory impairment (n = 8). In the 11 patients who underwent right heart catheterization before and after the initiation of therapy, the mean pulmonary artery pressure decreased significantly from 19.5 ± 5.5 mmHg to 14.3 ± 3.0 mmHg (P = 0.023) and the transpulmonary pressure gradient decreased significantly from 10.9 ± 4.6 mmHg to 7.2 ± 3.3 mmHg (P = 0.046). Of the 18 patients who started vasodilator therapy before the Fontan procedure, 10 survived surgery, 4 are awaiting surgery, 3 had not been evaluated for the Fontan procedure at the end of the study period, and 1 died of heart failure after discontinuing bosentan therapy. There were no deaths among the patients who started therapy after the Fontan procedure. Two of the 14 patients receiving bosentan discontinued treatment because of adverse effects (hepatic dysfunction and increased serum brain natriuretic peptide level). Bosentan or sildenafil therapy is usually safe and may contribute to reducing pulmonary vascular resistance in patients with a functionally single ventricle before and after a Fontan type operation.

Management of pulmonary vasodilator therapy in patients with pulmonary arterial hypertension during critical illness.

Pulmonary arterial hypertension (PAH) is commonly treated with pulmonary arteriolar vasodilator therapy. When a patient on PAH medication is admitted to intensive care, determining how to manage their medication during the critical illness is often complicated. There may be considerations related to the inability to take medication by mouth, related to acute renal failure or acute liver injury, related to altered mental status or delirium, or related to hypotension and bacteremia. Decisions of how to manage these medications can have a major impact on the patient’s clinical course. Presently, provider experience is the major tool in navigating the decisions regarding these medications. In this review, we offer our recommendations of how to manage PAH patients with critical illness who are on PAH medications. These recommendations include how to deliver medications via feeding tubes, how to dose medications in the setting of acute renal failure or acute liver failure, and how to manage medications during hypotension or when a tunneled catheter needs to be removed.

Oral vasodilator therapy in patients with moderate to severe portopulmonary hypertension as a bridge to liver transplantation

Portopulmonary hypertension (POPH) is a part of group 1 pulmonary hypertension (pulmonary hypertension associated with portal hypertension). Liver transplantation (LTx) may be curative, but is usually restricted to patients with mild-to-moderate POPH. The presence of severe POPH may be a contraindication to transplantation because of the elevated risk of peritransplantation and post-transplantation morbidity and mortality. This report describes a series of seven patients with onset of moderate (two patients) or severe (five patients) POPH before LTx, of whom six were treated with oral vasodilator therapy for POPH. Although previous studies recommend aggressive parenteral prostacyclin therapy (epoprostenol), we describe the opportunity to treat cases of severe POPH with an oral phosphodiesterase type 5 inhibitor (sildenafil) and/or an endothelin receptor antagonist (bosentan/ambrisentan) as a bridge to successful LTx in selected patients.

Right Ventricular Function Predicts Clinical Response to Specific Vasodilator Therapy in Patients with Pulmonary Hypertension

We followed patients with pulmonary arterial hypertension (PAH) receiving specific vasodilator therapy and tested for predictors of clinical outcome. Thirty-two patients (mean age 39 ± 15 years, 22 women, diagnosed with pulmonary hypertension; PH): 29 with PAH and 3 patients with inoperable chronic thromboembolic PH received therapy with either bosentan, sildenafil, or both and were evaluated with clinical parameters, biomarkers (B-type natriuretic peptide values), and echocardiography before receiving specific medication and every 3 months thereafter. A right heart catheterization was performed at baseline. A composite endpoint of death, worsening of functional class, or the need of a second vasodilator agent was used to define the clinical nonresponders. Patients were followed for 14 months (7.5-21). The endpoint was reached by 15 patients: four patients died (two idiopathic PAH and two PAH in context of Eisenmenger syndrome), seven patients showed 1 functional class worsening, and four patients needed to be switched to combination therapy. Patients who remained clinically stable or improved had at baseline a better cardiac output with a less remodeled right ventricle (RV) and better functioning RV (all P < 0.05). A RV fractional area change (RVFAC) lower than 25.7% and a RV global strain value higher than -13.4% predict with 87% sensitivity and 83% specificity (AUC 87.3%, P = 0.001) and 73% sensitivity and 91% specificity (AUC 84.2%, P = 0.003), respectively, patients who will deteriorate clinically under specific vasodilator therapy. A multivariate model showed RVFAC to be the only independent predictor of the endpoint with a HR of 0.87 (0.8-0.96), P = 0.007. Over an average period of 1 year, almost half of patients showed signs of clinical deterioration despite specific vasodilator therapy. Parameters of right ventricular morphology and function had prognostic value in these patients.

Effects of Vasodilation in Heart Failure With Preserved or Reduced Ejection Fraction: Implications of Distinct Pathophysiologies on Response to Therapy

The purpose of this study was to compare hemodynamic responses to vasodilator therapy in patients with heart failure (HF) and preserved ejection fraction (HFpEF) versus HF and reduced ejection fraction (HFrEF). There is no proven therapy for HFpEF. In the absence of data, medicines with established benefit in HFrEF such as vasodilators are frequently prescribed for HFpEF. We compared baseline hemodynamics and acute responses to vasodilation with intravenous sodium nitroprusside in patients with HFrEF (n = 174) and HFpEF (n = 83), determined invasively by cardiac catheterization. Baseline blood pressure, stroke volume, and cardiac output were greater in HFpEF than HFrEF, while pulmonary artery mean and pulmonary wedge pressures were similar. Left ventricular filling pressures were reduced to a similar extent in each group with nitroprusside, but the drop in systemic arterial pressure was 2.6-fold greater in HFpEF (p < 0.0001), and improvements in stroke volume and cardiac output were each ∼60% lower in HFpEF compared to HFrEF (p < 0.0001). Despite similarly elevated filling pressures, HFpEF patients were fourfold more likely than HFrEF to experience a reduction in stroke volume with nitroprusside (p < 0.0001), suggesting greater vulnerability to preload reduction. Pulmonary artery systolic pressure dropped more in HFpEF than in HFrEF despite similar reduction in pulmonary mean pressure and resistance, suggesting higher right ventricular systolic elastance in HFpEF. As compared to patients with HFrEF, patients with HFpEF experience greater blood pressure reduction, less enhancement in cardiac output, and greater likelihood of stroke volume drop with vasodilators. These findings emphasize fundamental differences in the 2 HF phenotypes and suggest that more pathophysiologically targeted therapies are needed for HFpEF.

Therapeutic potential of sildenafil in patients with heart failure and reactive pulmonary hypertension

The PDE5 inhibitor sildenafil belongs to the established and approved therapies in pulmonary arterial hypertension (PAH) [1]. While PAH is a relatively rare disease, pulmonary hypertension (PH) due to left heart disease (postcapillary PH; group 2 of the Dana Point classification) is a frequent phenomenon, particularly in patients with congestive heart failure (CHF) [2]. Importantly, in patients with left heart disease the presence of PH and an impaired right ventricular (RV) function, indicating biventricular heart failure, is associated with a particularly poor prognosis [2]. Targeted PAH therapy is currently not recommended in postcapillary PH [1]. However, in patients with severe CHF who present with impaired RV function and PH despite optimized medical therapy, additional treatment of PH may improve exercise tolerance and outcome. Small uncontrolled studies indicate that sildenafil may be beneficial in patientswith CHF [3,4], but these studies did not consider the severity of PH and the extent of prevs. postcapillary pressure elevation. In this context, the current ESC/ERS guidelines on PH distinguish between passive and reactive postcapillary PH, depending on the transpulmonary gradient (TPG). The therapeutic consequence of this hemodynamic definition remains unclear, however patients with a predominant precapillary component of PH may benefit from targeted therapy. In the context of compassionate care, 9 highly selected patients with biventricular heart failure (LVEF b40%; impaired RV function, defined as TAPSE b17 mm; NYHA class III/IV) and reactive PH (PAPmean ≥25 mmHg), characterized by elevated left ventricular filling pressures (PCWP/LVEDP ≥15 mmHg) and an increased TPG (N12 mmHg) were treatedwith sildenafil (20 mg tid) in addition to pre-existing, guidelineoriented treatment of CHF which had been on a stable dose for at least one month. In all patients, right heart catheterization was performed before and after initiation of sildenafil. Additionally, echocardiographic parameters, serummarkers (NTproBNP) and exercise capacity (6MWD) were recorded. The mean age of the patients was 67.4±2.2 years (range 64–75 years). 7 patients were initially in NYHA class III, 2 patients in NYHA class IV. All patients had received best medical treatment for CHF according to current guidelines (β-blockers, ACE inhibitors and/or AT1-receptor antagonists, aldosterone antagonists, diuretics). The mean follow-up after initiation of sildenafil was 19.7±6.9 weeks. The effects of sildenafil on invasive hemodynamics, echocardiographic parameters, serum markers and exercise capacity are summarized in Table 1. Add-on sildenafil treatment particularly resulted in a significant decrease of PAPmean, TPG and PVR as well as a decrease of PCWP and a trend towards decreased SVR. These hemodynamic changes were associated with an improvement of prognostically relevant parameters including an increase of RV function, decreased right atrial and right ventricular dimensions, a reduction of NTproBNP serum levels, and a substantial improvement of the 6MWD by 91±54m. Consistently, the patients clinical status improved markedly, and there were no significant adverse events. In highly selected patients with CHF, PH and impaired RV function, who were characterized by a predominant precapillary component of PH, the PDE5 inhibitor sildenafil significantly improved clinical symptoms, exercise capacity and prognostically relevant parameters. Although these findings suggest a beneficial effect in this special group of patients, they have to be interpreted with great caution. While the extent of the precapillary component in such patients is highly variable and depends on the volume load, it is important to note that all measurements were performed in fully compensated condition, so that the body weight remained unchanged between the first and follow-up hemodynamic measurements (75.0±6.4 vs. 74.8±6.0 kg, n.s.). Furthermore, previous mortality data exist on the effects of pulmonary vasodilator therapy in patients with CHF. In the FIRST trial, treatment with epoprostenol was associated with a higher mortality compared to placebo [5], indicating that pulmonary vasodilationmay be detrimental in CHF. However, there are important differences between this observation and the findings presented

Section 14: Managing Patients With Hypertension and Heart Failure

Section 14: Managing Patients With Hypertension and Heart Failure

Long-term hemodynamic responses to vasodilator therapy in patients with severe left ventricular dysfunction

Maximal oral vasodilator therapy resulted in long-term reduction of initially elevated pulmonary vascular resistance in 10 of 13 patients with severe heart failure who tolerated inotrope-supported uptitration of afterload reduction. Eleven patients were unable to tolerate vasodilator therapy and required inotropic support for successful cardiac transplantation.

Effects of long-term vasodilator therapy in patients with carotid sinus hypersensitivity

Background In patients affected by carotid sinus hypersensitivity, long-term vasodilator therapy might increase the risk of syncopal episodes by reducing systolic blood pressure and venous return to the heart.Methods and Results Thirty-two patients (mean age 73 ± 9 years; 20 men) who met all the following criteria were included: (1) one or more episodes of syncope occurring during long-term (>6 months) treatment with angiotensin-converting enzyme inhibitors, long-acting nitrates, calcium antagonists, or a combination of these; (2) a positive response to carotid sinus massage, defined as the reproduction of spontaneous syncope in the presence of ventricular asystole ≥3 seconds or a fall in systolic blood pressure ≥50 mm Hg; (3) negative workup for other causes of syncope. The patients were randomly assigned to continue or to discontinue use of vasodilators; carotid sinus massage was repeated 2 weeks after randomization. By the end of the study period, the baseline values of systolic blood pressure were significantly different between the 2 groups of patients both in supine (P =.01) and upright (P =.03) positions. Syncope had been induced by carotid sinus massage in 81% of patients in the “on-vasodilator” group and in 62% of patients in the “off-vasodilator” group (P =.21). The cardioinhibitory reflex was of similar magnitude in the 2 groups, being found in 50% of the patients in each group, with a maximum ventricular pause of 7.1 ± 2.7 and 6.7 ± 1.8 seconds, respectively. The percentage decrease of blood pressure did not differ between the 2 groups, even if, in absolute values, the baseline difference of blood pressure roughly persisted for the duration of the test. In consequence of that, the rise of blood pressure to similar values was delayed approximately 30 seconds in the “on-vasodilator” group and took more than 2 minutes to return to baseline values.Conclusions In patients affected by carotid sinus hypersensitivity, chronic vasodilator therapy does not have a direct effect on carotid sinus reflexivity, although the delayed recovery of pretest blood pressure values could indirectly potentiate the severity of the clinical manifestations of the syndrome. The persistence of hypotension for a longer time after the end of the massage suggests that vasodilators cause an impairment of compensatory mechanisms. (Am Heart J 1998;136:264-8.)

Response of Symptomatic Myocardial Ischemia in Ischemic Cardiomyopathy to Intensive Vasodilator Therapy

To determine the cardiovascular protective effects of angiotensin-converting enzyme inhibitors, we examined the response to intensive vasodilator therapy in patients with ischemic cardiomyopathy and ongoing angina pectoris. We found that for patients with ischemic cardiomyopathy and ongoing active angina, intensive vasodilator therapy with angiotensin-converting enzyme inhibition and nitrates improved not only heart failure-related symptoms, but also resulted in a significant improvement in symptomatic ischemia and ischemia-related morbid events.

Changing vasomotor responses of coronary arteries to nifedipine

Coronary vasomotion is influenced by a variety of factors, including atherosclerosis and diurnal variations in α-adrenergic tone. The effect of such factors on the coronary response to vasodilator drugs is unknown. To determine whether there is a diurnal variation to the response of coronary arteries to nifedipine, and whether this response is altered by atherosclerosis, we studied 11 patients with smooth coronary arteries, six in the morning and five in the afternoon, and 12 patients with irregular coronary arteries,, six in the morning and six in the afternoon. Changes in coronary blood flow and the vasomotor response of an epicardial coronary artery were measured before and after a 2 mg intracoronary infusion of nifedipine. There were no appreciable differences in epicardial vessel dilator response or coronary blood flow in the morning and afternoon among patients with smooth coronary arteries. By contrast, patients with irregular coronary arteries, had a significantly diminished dilator response in the afternoon, without an appreciable change in coronary blood flow. We postulate that normal coronary arteries maintain basal tone throughout the day. By contrast, atherosclerotic coronary arteries cannot do the same, increasing tone in the morning in response to catecholamines. When catecholamine levels drop in the afternoon, basal tone decreases in atherosclerotic vessels, and the dilator response to nifedipine is blunted. This observation may have an important impact on the expected benefits and timing of vasodilator therapy in patients with coronary artery disease.