The noninvasive evaluation of a patient starts with clinical examination. Patients who are using pulmonary vasodilator pharmacologic therapy have a distinct facial flushing which can mask effects of systemic arterial vasoconstriction due to low systemic cardiac output (and at times can simulate distributive physiology). Use of sphygmomanometric response of systemic blood pressure to valsalva maneuver is extremely useful in estimating pulmonary capillary wedge pressure (PCWP) [11]. Inflation of brachial cuff to blood pressure 15 points higher than systemic arterial systolic blood pressure, performance of valsalva maneuver for up to 10 s and observation of phase 2 response allows for reliable and reproducible estimation of PCWP. Normally, Korotkoff sounds are heard during the initial phase of Valsalva then stop and return again at the end of Valsalva (phase 2). The persistence of Korotkoff sounds for either ≥4 beats but <10 s after the start of Valsalva, or for ≥10 s (“square root response”) predicts elevated PCWP. Jugular venous pulsations (JVP) are elevated, at times with prominent “v” waves if significant tricuspid regurgitation is present. An elevated JVP signifies an elevated RV end diastolic pressure and hence RV failure and poor prognosis. Venous hypertension can also be examined by provoking the abdominojugular reflux sign, which indicates a volume-overloaded state and limited compliance of the systemic venous system. The abdominojugular reflux sign is provoked by applying consistent pressure over the right upper abdominal quadrant, for at least 10 s. A sustained rise of >3 cm in the venous pressure for at least 15 s is a positive response [12]. It is also important to note how quickly the JVP “falls” when the abdominal pressure is removed to assess the compliance of the systemic venous system.

Clubbing may be present and is a marker of chronic hypoxemia. The RV is anteriorly positioned, directly behind the sternum and chest wall; a palpable “right ventricular” heave is variably present when it is enlarged. Auscultation may include a loud pulmonary component of the second heart sound (P2), a holosystolic murmur of tricuspid regurgitation, a diastolic murmur of pulmonary insufficiency and a third sound of RV origin. Tricuspid regurgitation in the setting of markedly elevated RV systolic pressure and an enlarged RV may produce a high-pitched murmur. Lung sounds are usually normal; “wet” crackles suggest elevated left ventricular end diastolic pressure, disease, while “dry” inspiratory crackles may point towards interstitial lung disease [13]. Hepatomegaly, elevated JVP, peripheral edema, ascites, and cool extremities are consistent with low output right heart failure, indicating more advanced disease.

A chest X-ray cannot be used for diagnosis of PH; however, certain findings can suggest important hemodynamics even though these findings are not sensitive or specific. An increased diameter of the right descending pulmonary artery may suggest significant elevated PAP. Increased hilar thoracic index (the horizontal distance between the outer borders of the right and left pulmonary arteries divided by the maximum transverse diameter of the thoracic cage. A ratio <0.35 is considered to be normal) is also suggestive of elevated PAP [14, 15]. In a prospective study of idiopathic pulmonary arterial hypertension (IPAH), the chest radiograph demonstrated prominence of the main pulmonary artery in 90 % of patients, enlarged hilar vessels in 80 %, and decreased peripheral vessels in 50 %. All three abnormalities were seen in just over 40 % of subjects, and the presence of all three abnormalities was associated with a higher mPAP and lower cardiac index [16]. The PCWP can be estimated by observing the vascular pattern and the presence of interstitial or alveolar edema on chest radiographs. It has been suggested that PCWP greater than 13 but less than 18 mmHg indicates the presence of vascular redistribution with relative hypervascularity of the upper lung fields. When PCWP is 18–25 mmHg, interstitial pulmonary edema is seen and when greater than 25 mmHg, alveolar edema and often pleural effusion is present [17, 18]. Such changes may be absent in the presence of remodeling changes within the pulmonary vascular bed.

CT scan and angiography are pivotal in diagnosing pulmonary embolism and chronic thromboembolic pulmonary hypertension (CTEPH), peripheral pulmonary arterial stenosis, and mechanical or other etiologies of obstruction within the pulmonary vasculature as causes of PH (as well as for ruling out significant primary parenchymal lung disease). However, for direct hemodynamic assessment of PH, CT has a limited role. Some CT findings that can predict hemodynamics include the main pulmonary artery (MPA) caliber, segmental artery to bronchus ratio [19, 20, 22], and presence of pericardial effusion [21]. MPA caliber greater than 29 mm measured 2 cm from the pulmonary valve has 84 % sensitivity, 75 % specificity, and 97 % positive predictive value for the presence of pulmonary arterial hypertension. Also, if the MPA has a maximum transverse diameter greater than that of the proximal ascending thoracic aorta, sensitivity is 70 %, specificity 92 %, and positive predictive value 96 % for the presence of pulmonary arterial hypertension. Segmental artery to bronchus ratio greater than 1.25 times the caliber of the adjacent bronchus suggests elevation of PAP [21] and pericardial thickening or effusion is suggestive of mPAP > 35 mmHg.

The use of MRI in management of patients with PH is evolving. Phase contrast MRI calculated pulmonary vascular index, acceleration time (defined as time from onset of PA forward flow to maximum velocity), the ratio between acceleration time and RV ejection time are being evaluated to calculate PAP but results have been variable [23]. Kuehne and colleagues showed that PVR assessment using MRI-guided catheterization and MRI velocity mapping provided more reproducible results than the traditional thermodilution method. In addition, this technique seems to provide the ability to sample PVR more comprehensively (including both overall and branch-specific resistance) than can be achieved using Doppler guidewires [24].

Electrocardiogram (ECG) lacks sensitivity and specificity in diagnosing PH. In patients with PH, sinus tachycardia may be the only abnormality present (EKG could be completely normal). RV strain, right ventricular hypertrophy (RVH), incomplete right bundle branch block and increased P wave amplitude are common findings [25]. On occasion, in patients in whom PAH attenuating treatment has been very effective, dramatic ECG changes from a pattern corresponding with RVH to a (near)-normal pattern have been reported [26]. P wave amplitude has been shown to predict prognosis in PAH [27].

The transthoracic echocardiogram (TTE) remains a core element of RV assessment with applications in the initial and longitudinal diagnosis and screening of pulmonary hypertension, discrimination between contributors to etiology, as well as in assessment of RV and valvular function. The European Society of Cardiology guidelines for the diagnosis and treatment of PH suggest the following: (1) PH is unlikely for tricuspid regurgitation velocity (TRV) ≤2.8 m/s, systolic PAP (sPAP) ≤ 36 mmHg (assuming RAP of 5 mmHg), and no additional echocardiographic signs of PH; (2) PH possible for TRV ≤ 2.8 m/s and sPAP ≤ 36 mmHg, but the presence of additional echocardiographic signs of PH or TRV of 2.9–3.4 m/s and SPAP of 37–50 mmHg with or without additional signs of PH; and (3) PH likely for TRV > 3.4 m/s and sPAP > 50 mmHg with or without additional signs of PH [3]. Combined with well-validated hemodynamic calculations, focused TTE can provide very close approximations of the pulmonary vascular and RV hemodynamics.

TTE-based estimation of sPAP most frequently relies upon determination of Doppler-based peak TVR and use of the modified Bernoulli equation (∆pressure = 4 × velocity [2]) to approximate differences between RV and right atrial (RA) pressure. Further addition of TTE-guided estimation of RA pressure (RAP) allows for calculation of RV systolic pressure (which in the absence of obstruction to RV outflow represents sPAP). As central venous pressure (CVP) and RAP are essentially equivalent in the absence of anatomic obstruction, the latter is commonly evaluated by measuring the size, flow patterns and the respiratory variation of the inferior vena cava (IVC). Generally, IVC diameter <2.1 cm and collapse greater than 50 % on inspiration would correspond to a normal RAP of 0–5 mmHg. The presence of either greater diameter or lesser collapse (but not both) correspond to RAP of 5–10 mmHg, and a diameter greater than 2.1 cm with less than 50 % collapse corresponds to a high RAP of 10–20 mmHg [28, 114]. These criteria are relatively poor indicators of RAP, however, and this should be acknowledged when estimating PAP [29]. Patients who cannot comply with taking a deep inspiration to demonstrate collapsibility of the IVC can be asked to perform a “sniff” maneuver, which causes a decrease in intrathoracic pressure.

Although widely accepted as a screening test, the precision of this echocardiographic estimate of PAP is modest. In studies that have compared echocardiographically estimated values and values measured by right heart catheterization (RHC), the mean difference ranged from 3 to 40 mmHg, and sPAP was underestimated with the echocardiographic method by >20 mmHg in 31 % of patients studied [30]. To minimize error in acquisition of the TR envelope by Doppler, it is recommended that TRV be measured in multiple views and the maximal velocity jet found should be used for the calculation. Inadequate regurgitant signals can be enhanced with the use of contrast. It should always be remembered that sPAP evaluation with Doppler methods, however, cannot definitively diagnose PH and has limited role in the decision to treat patients or to monitor therapy efficacy.

The simplest method of calculating the mPAP may be by using sPAP as follows:

As the only variable in the above equation is sPAP, this calculation carries the same pitfalls as measurement of sPAP mentioned above.

Doppler-based measure of diastolic pulmonary valve regurgitation may be difficult to obtain, and therefore may be absent on particular studies. When present and complete, use of the peak pulmonary valve regurgitation velocity (typically early in diastole) in the modified Bernoulli equation allows estimation of peak pressure difference between RV and PA in early diastole. The peak pulmonic regurgitation velocity represents the diastolic pressure gradient between the pulmonary artery and the RV. Adding the RAP to such calculation often provides acceptable estimation of mPAP (mPAP = 4 × (peak pulmonic valve regurgitation jet velocity)² + RAP) [32].

Application of the modified Bernoulli equation to the end-diastolic pulmonary regurgitation velocity allows estimation of the end-diastolic gradient between the RV and PA, which, when added to the TTE-based estimation of RA pressure, estimates diastolic PA pressure, (dPAP), with a high correlation with invasive dPAP measurements [34]. Similar estimation can be obtained by Doppler-based assessment of the earliest systolic gradient at the time of pulmonary valve opening (closely approximating end-diastolic gradient between RV and PA) and adding TTE-based estimation of RA pressure, yielding estimate of dPAP [35, 36].

In the evaluation of patients with PH, RHC is usually indicated for the following [2, 3]

RHC may have limited benefit when an alternative diagnosis is obvious on non-invasive testing. Similarly, RHC may have specific but limited use when elevated PAP pressures on non-invasive testing can be explained by left heart disease, diastolic dysfunction, or chronic lung disease.

Table 10.4 lists the essential components of invasive hemodynamic assessment of PH. The addition of exercise testing, vasoreactivity testing or fluid challenge, and angiography to RHC is discussed in appropriate sections below.

It is not infrequent that assessment of coronary anatomy may carry import implications when performed as part of RHC to evaluate PH. The reasons for such include, but are not limited to, evaluation of the coronary anatomy as part of surgical planning, presence of coronary-fistula to the right-sided chambers as a possible source of left to right shunt, presence of atherosclerotic coronary artery disease as a possible reason for impaired LV function or elevated filling pressure, and evaluation of the anatomic relations between the coronary arteries and the pulmonary arteries for specific procedures (e.g., percutaneous prosthetic pulmonary valve implantation).

RHC, although technically demanding, is a safe procedure when performed by experienced operators [54]. Hoeper and colleagues reported on 5,727 RHC procedures retrospectively and 1,491 prospectively, for a total of 7,218 procedures. The overall number of serious adverse events was 76 (1.1 %, 95 % confidence interval 0.8–1.3 %). The most frequent complications were related to venous access (e.g., hematoma, pneumothorax), followed by arrhythmias and hypotensive episodes related to vagal reactions or pulmonary vasoreactivity testing. The vast majority of these complications were mild to moderate in intensity and resolved either spontaneously or after appropriate intervention. Four fatal events were recorded in association with any of the catheter procedures, resulting in an overall procedure-related mortality of 0.055 % (95 % confidence interval 0.01–0.099 %). Of the four fatal complications only two were related to the procedure itself (PA rupture and both electromechanical dissociation and intrapulmonary hemorrhage) [55]. Adequate patient preparation such as management of anticoagulation issues can help in reducing vascular access complications. It should be remembered that RHC as an elective, planned procedure is a very safe procedure and is very different from placement of a pulmonary artery catheter (PAC) in patients admitted to the intensive care unit (ICU) where the use of PAC has, in some studies, been associated with increased mortality. Also while a PAC placed in an ICU patient may stay in situ for several days, thus increasing vascular, infectious, and thromboembolic complications, diagnostic RHC is typically a short outpatient procedure lasting under an hour.

Policy regarding fasting status of patients, use of peripheral IV, and withholding of particular medications (such as hypoglycemics, vasodilators, diuretics, or anticoagulants) should be dependent upon individual laboratory preference, health status of the patient, and whether sedative use is planned. A clear plan for such though, should be constructed and documented. For example, the calculation of risk-benefit ratio of sustaining therapeutic INR up until catheterization for an individual patient in whom anticoagulation has been prescribed for mechanical mitral valve and atrial fibrillation may well be different than that of another patient in whom warfarin is prescribed for primary prevention of stroke with atrial fibrillation. Clear description of such logic should be available to personnel within the team assisting in catheterization (Table 10.5).

While concern has been raised regarding safety and influence of sedatives used during catheterization on medical status and physiologic indices including loading conditions and inotropy, this is probably of minor concern unless liver and kidney functions are significantly impaired [57–59]. Nonetheless, it is becoming more common practice to avoid standard use of systemic sedation prior to or during RHC.

Complex influences by mechanical ventilation must be considered when assessing measured hemodynamics. Positive pressure ventilation, particularly in the setting of PEEP, variably increases RV afterload with resultant decline in RV contractility, and can contribute to elevated measure of PCWP particularly during inspiration [60, 61]. Additional influences may include baseline vascular and myocardial loading conditions and compliance of the chest wall and lungs. General practice is to discount meaningful influence of PEEP <10 cm H₂O on measured PCWP, with correction of PCWP when PEEP ≥10 cm H₂O by 2–3 cm for every 5 cm H₂O increment in PEEP [62, 63]. Another cause of falsely elevated PCWP in a mechanically ventilated patient is the monitoring catheter being located outside zone 3 (during positive pressure ventilation less of the lung is zone 3 due to elevated alveolar pressures). Care should be taken to demonstrate catheter tip placement within zone 3, gravitationally below the level of the left atrium [64].

Hemodynamic pressure measurements should reflect the time of most neutral intrathoracic pressure (in spontaneously respiring patients this occurs at end expiration, with converse in patients utilizing positive pressure ventilation), rather than sole recording of mean pressure. Esophageal manometry is rarely utilized to estimate the effects of high swings of intrathoracic pressure seen with labored breathing. When possible, the patient should be instructed to expire slowly to allow pressure recording that may assist in accuracy of hemodynamic measure [72].

Commonly used access sites include internal jugular (IJ) vein, femoral vein, brachial vein, and subclavian vein. Knowledge of prior procedures, venous and arterial obstructions, compressions, complex anatomical course and prior procedural complications is necessary to choose access site in an individual patient. The IJ vein is usually the preferred site because of its ease of access, lower complication rate and because it allows patients to be discharged early after procedure [54, 55, 65]. Proximal arm veins provide ready access to RHC, but catheter manipulation may be difficult and catheter size choice is limited. Some operators may prefer femoral vein if concomitant left heart catheterization is planned via femoral artery. Ultrasound guidance should be considered for both IJ and femoral access sites. Patients with kidney disease, congenital heart disease, pacemakers, or prior indwelling venous access for other reasons (e.g., TPN) are more likely to have had multiple prior procedures and consequent vascular injury or thrombosis. Imaging of the vascular bed may be established by various modalities (ultrasound, computed tomography and magnetic resonance angiography) and should be considered by the operator when deemed appropriate. The use of a micropuncture kit with a 21-gauge needle and introducer can minimize potential trauma from inadvertent puncture of the carotid artery. Table 10.6 lists the advantages and disadvantages of different catheterization access sites.