Pulmonary hypertension secondary to left ventricular systolic dysfunction: Contemporary diagnosis and management

Pulmonary hypertension secondary to left ventricular systolic dysfunction is often a poor prognostic marker in chronic heart failure. In this article, we review evidence supporting modern strategies addressing pulmonary hypertension in patients with left ventricular systolic dysfunction, including right-sided heart catheterization with vasoreactivity testing and subsequent parenteral, oral, and inhaled therapy. We delineate a diagnostic approach to secondary pulmonary hypertension and outline evidence-based therapeutic strategies for management in acute and chronic heart failure.     

Progressive left ventricular noncompaction and systolic dysfunction

Left ventricular noncompaction is a condition characterized by prominent ventricular trabeculations, often accompanied by systolic dysfunction. The present case involves an adult with a small ventricular septal defect, initially exhibiting mild systolic dysfunction and slightly prominent left ventricular trabeculations progressing over 13 years to severe dilated cardiomyopathy and overt noncompaction. The present case strongly suggests a correlation between the extent of noncompaction and the degree of systolic dysfunction. The initial presence of a small ventricular septal defect and mild trabeculations highlights the genetic determinants of non-compaction and the importance of closely following patients with mild noncompaction due to the possibility of progression. More sensitive diagnostic criteria are needed to avoid overlooking mild cases, which may show prominent trabeculations without reaching a requisite ratio of compacted to noncompacted tissue.     

Influence of hypertension, left ventricular hypertrophy, and left ventricular systolic dysfunction on plasma N terminal proBNP

OBJECTIVES: To examine the relation between plasma concentration of the N terminal of the precursor of brain natriuretic peptide (NT proBNP), left ventricular hypertrophy (LVH), and left ventricular systolic dysfunction (LVSD) in patients with a history of hypertension. DESIGN: Prospective study. SETTING: Teaching hospital based study. PATIENTS: NT proBNP concentrations were determined in five groups of individuals. Group 1: 15 echocardiographic normal controls; group 2: 22 patients with hypertension, normal left ventricular systolic function, and no LVH; group 3: 24 patients with hypertension, normal left ventricular systolic function, and LVH; group 4: 13 patients with history of hypertension, no history of ischaemic heart disease, and left ventricular wall motion index (WMI) between 1.9-1.3; and group 5:17 patients with a history of hypertension, no history of ischaemic heart disease, and WMI < 1.2. RESULTS: Median (range) NT proBNP concentrations (in fmol/ml) for groups 1-5, respectively, were: 129.4 (53.6-159.7), 147.4 (54.3-730. 5), 137.1 (35.8-403.9), 356.7 (124.4-934.4), and 493.5 (248.9-909). Mean log NT proBNP differed among all five groups (p < 0.0001), and between groups 4 and 5 versus groups 1-3 (p < 0.0001), and group 4 versus group 5 (p = 0.02) only. CONCLUSIONS: The results suggest that the presence of hypertension with or without LVH (and normal left ventricular systolic function) does not affect NT proBNP concentrations. Moreover, there is a significant rise in NT proBNP only when LVSD develops in hypertension. Thus, NT proBNP remains a useful diagnostic aid for LVSD, even in hypertensive patients.     

Asymptomatic left ventricular systolic dysfunction in essential hypertension: prevalence, determinants, and prognostic value

Prevalence, determinants, and prognostic value of asymptomatic left ventricular systolic dysfunction (LVSD) in uncomplicated subjects with essential hypertension are still incompletely known. We studied 2384 initially untreated subjects with hypertension, no previous cardiovascular disease, and no symptoms or physical signs of congestive heart failure (CHF). These subjects were studied at entry and followed for up to 17 years (mean 6.0). Asymptomatic LVSD (ALVSD), defined by an echocardiographic ejection fraction <50%, was found in 3.6% of subjects. Cigarette smoking (P=0.013), increased left ventricular (LV) mass (P=0.001), and higher 24-hour heart rate (P=0.014) were independent correlates of ALVSD. During follow-up, a first cardiovascular event occurred in 227 subjects, and 24 of these events were hospitalizations for symptomatic CHF. Incidence of CHF per 100 persons per year was 0.12 in patients without and 1.48 in patients with ALVSD (log-rank test P=0.0001). In a Cox model, after adjustment for age (P=0.0001), LV mass (P=0.0001), and cigarette smoking (P=0.039), LVSD conferred a markedly increased risk for CHF (odds ratio, 9.99; 95% confidence interval, 3.67 to 27.2). Incidence of coronary (0.84 versus 0.62x100 person years) and cerebrovascular (0.80 versus 0.62x100 person years) events did not differ (all P=NS) between subjects with and without ALVSD. ALVSD is a potent and early marker of evolution toward severe CHF requiring hospitalization in subjects with essential hypertension.     

Time course and mechanisms of left ventricular systolic and diastolic dysfunction in monocrotaline-induced pulmonary hypertension

Although pulmonary hypertension (PH) selectively overloads the right ventricle (RV), neuroendocrine activation and intrinsic myocardial dysfunction have been described in the left ventricle (LV). In order to establish the timing of LV dysfunction development in PH and to clarify underlying molecular changes, Wistar rats were studied 4 and 6 weeks after subcutaneous injection of monocrotaline (MCT) 60 mg/kg (MCT-4, n = 11; MCT-6, n = 11) or vehicle (Ctrl-4, n = 11; Ctrl-6, n = 11). Acute single beat stepwise increases of systolic pressure were performed from baseline to isovolumetric (LVPiso). This hemodynamic stress was used to detect early changes in LV performance. Neurohumoral activation was evaluated by measuring angiotensin-converting enzyme (ACE) and endothelin-1 (ET-1) LV mRNA levels. Cardiomyocyte apoptosis was evaluated by TUNEL assay. Extracellular matrix composition was evaluated by tenascin-C mRNA levels and interstitial collagen content. Myosin heavy chain (MHC) composition of the LV was studied by protein quantification. MCT treatment increased RV pressures and RV/LV weight ratio, without changing LV end-diastolic pressures or dimensions. Baseline LV dysfunction were present only in MCT-6 rats. Afterload elevations prolonged τ and upward-shifted end-diastolic pressure dimension relations in MCT-4 and even more in MCT-6. MHC-isoform switch, ACE upregulation and cardiomyocyte apoptosis were present in both MCT groups. Rats with severe PH develop LV dysfunction associated with ET-1 and tenascin-C overexpression. Diastolic dysfunction, however, could be elicited at earlier stages in response to hemodynamic stress, when only LV molecular changes, such as MHC isoform switch, ACE upregulation, and myocardial apoptosis were present. J. Correia-Pinto and T. Henriques-Coelho contributed equally to this work.     

Subclinical left ventricular longitudinal systolic dysfunction in hypertension with no evidence of heart failure

BACKGROUND: The prevalence of subclinical left ventricular (LV) systolic dysfunction in asymptomatic hypertensive patients was determined using tissue Doppler imaging (TDI). METHODS AND RESULTS: TDI-derived mitral annular velocities were acquired in 35 control subjects, 92 asymptomatic hypertensive patients with no heart failure (HHD), and 15 patients with diastolic heart failure (DHF). No significant intergroup differences in LV ejection fraction were noted. Peak systolic annular velocity was significantly reduced in the DHF group compared with the control and HHD group. Using peak systolic velocity <6.1 cm/s as a cut-off value for abnormal velocity, 10% of HHD patients and 53% of DHF showed impaired LV longitudinal systolic velocity. Peak early diastolic annular velocities were significantly reduced in both the HHD and DHF groups compared with the control group. With multivariable regression analysis, peak early and late diastolic annular velocities, female gender and deceleration time of the E wave velocity were selected as independent predictors for peak systolic annular velocities. CONCLUSIONS: Systolic long-axis LV function was impaired in 10% of asymptomatic hypertensive patients. Its reduction was closely correlated with impaired diastolic function. Assessment of LV longitudinal function by TDI plays an important role in identifying diastolic dysfunction and subclinical LV systolic dysfunction in asymptomatic hypertensive patients.     

Left ventricular mass and systolic dysfunction in essential hypertension

A relation between left ventricular (LV) hypertrophy and depressed midwall systolic function has been described in hypertensive subjects. However, a strong confounding factor in this relation is concentric geometry, which is both a powerful determinant of depressed midwall systolic function and a correlate of LV mass in hypertension. To evaluate the independent contribution of LV mass to depressed systolic function, 1827 patients with never-treated essential hypertension (age 48 +/- 12 years, men 58%) underwent M-mode echocardiography under two-dimensional guidance. Relative wall thickness was the strongest determinant of low midwall fractional shortening (r = -0.63, P < 0.0001). The significant inverse relation observed between LV mass and midwall fractional shortening (r = -0.43, P < 0.0001) persisted after taking into account the effect of relative wall thickness (partial r = -0.27, P < 0.0001). Within each sex-specific quintile of relative wall thickness, prevalence of subnormal afterload-corrected midwall systolic function was greater in subjects with, than in subjects without, LV hypertrophy (P < 0.05 for the first, third, fourth and fifth quintile). In a multiple linear regression analysis, both LV mass (P < 0.0001) and relative wall thickness (P < 0.0001) were independent predictors of a reduced midwall fractional shortening. In conclusion, the inverse association between LV mass and midwall systolic function is partly independent from the effect of relative wall thickness. LV hypertrophy is a determinant of subclinical LV dysfunction independently of the concomitant changes in chamber geometry.     

Myocardial strain to detect subtle left ventricular systolic dysfunction

In daily clinical practice, LV systolic function is routinely assessed with the use of two‐dimensional echocardiography. Using biplane LV end‐diastolic and end‐systolic volumes, LVEF is calculated. The introduction of real‐time three‐dimensional echocardiography has improved the accuracy of echocardiographic assessment of LVEF. However, calculated LVEF may not truly represent LV systolic function in specific cardiac diseases or when subtle LV dysfunction is present. Two‐dimensional speckle tracking echocardiography enables assessment of myocardial strain, thereby providing detailed information on global and regional LV deformation. This is of particular interest when subtle LV systolic dysfunction is present despite preserved LVEF. In this review, the potential use of LV global longitudinal strain to detect subtle LV systolic dysfunction is illustrated in various clinical scenarios.     

Long-term significance of Killip class and left ventricular systolic dysfunction

Background

Killip classification is an independent predictor of early mortality after myocardial infarction, and the presence of left ventricular systolic dysfunction (left ventricular ejection fraction <50%) and high Killip class predicts poor short-term prognosis. The long-term prognostic significance of Killip class and left ventricular systolic dysfunction, however, is unknown.

Methods

We studied the impact of Killip class and left ventricular systolic dysfunction on all-cause mortality (assessed in May 2007 using the Social Security Death Index) in myocardial infarction patients admitted from July 1995 to December 1996.

Results

Of 282 patients, 60% (n = 168) were Killip class 1, 23% (n = 64) were Killip class 2, and 17% (n = 50) were Killip class 3 or 4. Patients with higher Killip class were older and more likely to have diabetes, a non-Q-wave myocardial infarction, renal insufficiency, chronic obstructive pulmonary disease, and left ventricular systolic dysfunction. There were 152 deaths at 10 years after myocardial infarction, and patients with Killip class 2, 3, or 4 had higher mortality compared with Killip class 1 in unadjusted analyses. Patients with left ventricular systolic dysfunction and Killip class of 2 or more had significantly higher 10-year mortality (70 deaths or 76.9%) compared with Killip class 1 patients without left ventricular systolic dysfunction (29 deaths or 34.5%, P <.001). This risk persisted after adjusting for demographics, cardiovascular risk factors, and co-morbidities. Much of the risk was explained by deaths in the first 5 years after myocardial infarction.

Conclusions

Killip class is a strong predictor of long-term mortality, and patients with high Killip class and left ventricular systolic dysfunction are at highest risk.     

Combined training in patients with systolic left ventricular dysfunction

The objective of the work was to evaluate the effect of eight-week combined training on the performance, aerobic capacity and basic haemodynamic parameters in patients with systolic dysfunction of the left ventricle and to assess its safety. The investigation comprised 26 patients, men mean age (x +/- SD) 61.8 +/- 11.1 years with coronarographically verified chronic ischaemic heart disease and with a left ventricular ejection fraction lower than 40% (EF 35 +/- 4%). Before the beginning and after completion of the rehabilitation programme (eight weeks) a spiroergometric examination was made, up to the symptom-limited maximum. Fitness elements were included after 2 weeks of aerobic training. The lesson lasted 60 mins. and included warming up (10 mins.), aerobic load on an ergometer with an intensity of the load at the level of the anaerobic threshold (20 mins.), the stage of fitness training on a combined training machine (20 mins) and the relaxation stage (10 mins). In the fitness stage the patients started to exercise at the 30% level, after two weeks at the 60% level 1-RM (one repetition maximum) The results showed after eight-week combined training a significant (p < 0.05) increase of the maximum achieved performance (from 104 +/- 27 to 132 +/- 32 W) in patients with systolic left ventricular dysfunction. There was a significant increase in the capacity of the transport system expressed by the value of the maximum oxygen uptake (from 1545 +/- 312 to 1740 +/- 359 ml.min-1) and MET (from 5.3 +/- 1.3 to 6.0 +/- 1.4). There was a significant decrease of the blood pressure at rest, systolic and diastolic, and of the baseline value of the heart rate at rest and of the "product rate, pressure"--RPP. Changes in the EF were not significant.     

阻塞性睡眠呼吸暂停低通气综合征与左心室收缩功能不全关系的研究

目的初步探讨阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea/hypopneasyndrome,OSAHS)对左心室收缩功能的影响。方法98例入选者分为OSAHS合并左室收缩功能不全组(试验组21例)、OSAHS无左室收缩功能不全组(OSAHS组47例)和无OSAHS、左室收缩功能不全组(对照组30例)。在多导睡眠图监测下,次晨抽取外周静脉血测定血浆内皮素(ET)。结果①试验组SpO2Low(整夜睡眠监测中患者最低脉搏血氧饱和度)低于另两组(P<0.05),平均呼吸暂停时间、%TST-SpO2<90%(一整夜睡眠监测中患者脉搏血氧饱和度低于90%时间占整个睡眠监测时间的百分比)、%TST-SpO2<80%、血浆ET含量均高于另两组(P<0.05);试验组和OSAHS组呼吸暂停低通气指数(AHI)、最长暂停时间无差异。②两组OSAHS患者血浆ET均与%TST-SpO2<90%(r=0.457,P=0.021;r=0.415,P=0.026)、%TST-SpO2<80%(r=0.372,P=0.016;r=0.334,P=0.031)呈正相关,试验组左室射血分数与%TST-SpO2<80%(r=-0.529,P=0.024)、血浆ET(r=-0.485,P=0.041)呈负相关。结论OSAHS患者反复长时间的呼吸暂停、中重度低氧血症和高水平血浆ET可能对左室收缩功能有重要的影响。     

阻塞性睡眠呼吸暂停低通气综合征与左心室收缩功能不全关系的研究

目的 初步探讨阻塞性睡眠呼吸暂停低通气综合征（obstructive sleep apnea/hypopnea syndrome,OSAHS）对左心室收缩功能的影响.方法 98例入选者分为OSAHS合并左室收缩功能不全组（试验组21例）、OSAHS无左室收缩功能不全组（OSAHS组47例）和无OSAHS、左室收缩功能不全组（对照组30例）.在多导睡眠图监测下,次晨抽取外周静脉血测定血浆内皮素（ET）.结果 ①试验组SpO2Low（整夜睡眠监测中患者最低脉搏血氧饱和度）低于另两组（P＜0.05）,平均呼吸暂停时间、%TST-SpO2〈90%（一整夜睡眠监测中患者脉搏血氧饱和度低于90%时间占整个睡眠监测时间的百分比）、%TST-SpO2〈80%、血浆ET含量均高于另两组（P＜0.05）;试验组和OSAHS组呼吸暂停低通气指数（AHI）、最长暂停时间无差异.②两组OSAHS患者血浆ET均与%TST-SpO2 〈90% （r=0.457,P=0.021;r=0.415,P=0.026）、%TST-SpO2〈80% （r=0.372,P=0.016;r=0.334,P=0.031）呈正相关,试验组左室射血分数与%TST-SpO2〈80% （r=-0.529,P=0.024）、血浆ET（r=-0.485,P=0.041） 呈负相关.结论 OSAHS患者反复长时间的呼吸暂停、中重度低氧血症和高水平血浆ET可能对左室收缩功能有重要的影响.